Publications

@article{ngwa2014radiation,

title = {Radiation Therapy Biomaterials for Response Assessment and Nodal Detection (Brand)},

author = {W Ngwa and Y Altundal and H Korideck and R Kumar and S Sridhar and R Cormack and M Makrigiorgos},

year  = {2014},

date = {2014-01-01},

journal = {International Journal of Radiation Oncology• Biology• Physics},

volume = {90},

number = {1},

pages = {S856},

publisher = {Elsevier},

abstract = {Purpose/Objective(s)

We propose that routinely used inert radiation therapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smart ones by incorporating multifunctional non-toxic gold nanoparticles (GNPs) for sustained in-situ release. Our hypothesis is that the GNPs released, after implantation of the smart biomaterial in tumor, can be programmed to label/brand metastatic or circulating tumor cells (CTCs) at their source before they are shed into hematogenous or lymphatic circulation. This would enable significantly enhanced CTCs detection by different methods. In this work, we developed and characterized such prototype smart biomaterials. We also assessed the potential for released GNPs to label/brand CTCs over time for enhanced detection by photoacoustic methods.

Materials/Methods

Prototype smart biomaterials were produced by coating inert fiducials with a polymer film loaded with GNPs. In vitro release of GNPs was monitored by UV-Vis Spectroscopy over time. An experimentally determined diffusion coefficient (D) for 10 nm nanoparticles in mouse prostate tumor model was employed to estimate D for other nanoparticle sizes using the Stoke-Einstein equation. The error function diffusion model in the experimental study was applied to calculate the diffusion time required to label any CTCs within the tumor volume. CTCs were considered labeled when in contact with an experimentally determined minimum GNPs concentration (37ng/g) detectable by photoacoustic methods. The study was done for a range of tumor sizes and initial concentrations.

Results

Our prototype smart biomaterial showed sustained customizable release of GNP in vitro, with release profile reaching steady state after 2 hours. Meanwhile, for the experimentally determined D, results using an initial concentration of 7 mg/g showed it would take 7.6-17.3 days for the released GNP to brand any CTCs located within the tumor volume of diameter 2-3 cm. The labeling time decreased with decrease in GNP size or increase in initial concentration.

Conclusions

Considered together, our results demonstrate potential for labeling CTCs right from the source tumor, with the labeling customizable through nanoparticle design: size, initial concentration, etc. The highest clinical impact of this innovative approach is anticipated in significantly enhancing the isolation and detection efficiency of CTCs in circulation or lymph nodes towards improved characterization of tumor aggressiveness, treatment response, or prognosis. The ability to brand and track CTCs right from their source could also lead to a better understanding of mechanisms contributing to cancer progression or metastasis. The innovative approach would come at no additional inconvenience to RT patients who are candidates for the currently used inert RT biomaterials.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cormack2014f,

title = {SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy},

author = {R Cormack and W Ngwa and S Tangutoori and K Rajiv and S Sridhar and G Makrigiorgos},

year  = {2014},

date = {2014-01-01},

journal = {Medical Physics},

volume = {41},

number = {6Part22},

pages = {389--390},

publisher = {American Association of Physicists in Medicine},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{petrovelectric,

title = {Electric Field Encephalography: Electric fields and their application to functional brain imaging.},

author = {Yury Petrov and Srinivas Sridhar},

year  = {2013},

date = {2013-07-03},

abstract = {We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision



},

keywords = {Neurotechnology},

pubstate = {published},

tppubtype = {article}

}

@article{yavuzcetin2013fabrication,

title = {Fabrication and characterization of single mode annealed proton exchanged waveguides in-x-cut lithium niobate},

author = {O Yavuzcetin and Nicholas R Perry and Sean T Malley and Rebecca L Dally and Herman P Novikov and Birol Ozturk and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

journal = {Optical Materials},

volume = {36},

number = {2},

pages = {372--375},

publisher = {North-Holland},

abstract = {Lithium niobate is a key, well-known material in optical communication that maintains its importance due to its high speed in electro-optical modulators and other optical devices. Using a benzoic acid proton exchange method and annealing in wet O2, we have fabricated waveguides along the y-axis of -x-cut lithium niobate substrate. We have optimized proton exchange and annealing time to make waveguides with the highest transmission we observed to date. The optical transmission was measured in waveguides between 3 μm and 7 μm in width, and 10 mm in length. The near-field mode properties of the waveguides were also examined. In addition, we discovered that the transmission through waveguides is reduced by the surface residues which are underestimated in most fabrication processes. This paper outlines the full fabrication process as well as characterization methods in detail, including a supercontinuum laser source.},

keywords = {Sensors},

pubstate = {published},

tppubtype = {article}

}

@article{ngwa2013vitro,

title = {In vitro radiosensitization by gold nanoparticles during continuous low-dose-rate gamma irradiation with I-125 brachytherapy seeds},

author = {Wilfred Ngwa and Houari Korideck and Amin I Kassis and Rajiv Kumar and Srinivas Sridhar and Mike G Makrigiorgos and Robert A Cormack},

year  = {2013},

date = {2013-01-01},

journal = {Nanomedicine: Nanotechnology, Biology and Medicine},

volume = {9},

number = {1},

pages = {25--27},

publisher = {Elsevier},

abstract = {This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources.

This communication reports the first experimental evidence of gold nanoparticle (AuNP) radiosensitization during continuous low-dose-rate (LDR) gamma irradiation with low-energy brachytherapy sources. HeLa cell cultures incubated with and without AuNP were irradiated with an I-125 seed plaque designed to produce a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at low-dose rates ranging from 2.1 to 4.5 cGy/h. Residual γH2AX was measured 24 h after irradiation and used to compare radiation damage to the cells with and without AuNP. The data demonstrate that the biological effect when irradiating in the presence of 0.2 mg/ml concentration of AuNP is about 70%–130% greater than without AuNP. Meanwhile, without radiation, the AuNP showed minimal effect on the cancer cells. These findings provide in vitro evidence that AuNP may be employed as radiosensitizers during continuous LDR brachytherapy.

},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{rivera2013fibronectin,

title = {Fibronectin and vitronectin promote human fetal osteoblast cell attachment and proliferation on nanoporous titanium surfaces},

author = {DM Rivera-Chacon and M Alvarado-Velez and CY Acevedo-Morantes and SP Singh and E Gultepe and D Nagesha and S Sridhar and JE Ramirez-Vick},

year  = {2013},

date = {2013-01-01},

journal = {Journal of biomedical nanotechnology},

volume = {9},

number = {6},

pages = {1092--1097},

publisher = {American Scientific Publishers},

abstract = {We studied the influence of the serum proteins fibronectin (FN) and vitronectin (VN) with nanoporous TiO2 on osteoblast cell attachment. Taken together, these results suggest that the nanoporous surface topography results in increased adsorbtion of FN and VN the slow release of these proteins are important factors in osteoblast attachment to titanium alloys.



Improvements in osteoconduction of implant biomaterials require focusing on the bone-implant interface, which is a complex multifactorial system. Surface topography of implants plays a crucial role at this interface. Nanostructured surfaces have been shown to promote serum protein adsorption and osteoblast adhesion when compared to micro-structured surfaces for bone-implant materials. We studied the influence of the serum proteins fibronectin and vitronectin on the attachment and proliferation of osteoblasts onto nanostructured titania surfaces. Human fetal osteoblastic cells hFOB 1.19 were used as model osteoblasts and were grown on nanoporous TiO2 templates, using Ti6Al4V and commercially pure Ti substrates as controls. Results show a significant increase in cell proliferation on nanoporous TiO2 over flat substrates. Initial cell attachment data exhibited a significant effect by either fibronectin or vitronectin on cell adhesion at the surface of any of the tested materials. In addition, the extent of cell adhesion was significantly different between the nanoporous TiO2 and both Ti6Al4V and commercially pure Ti substrates, with the first showing the highest surface coverage. There was no significant difference on osteoblast attachment or proliferation between the presence of fibronectin or vitronectin using any of the material substrates. Taken together, these results suggest that the increase in osteoblast attachment and proliferation shown on the nanoporous TiO2 is due to an increase in the adsorption of fibronectin and vitronectin because of the higher surface area and to an enhanced protein unfolding, which allows access to osteoblast binding motifs within these proteins.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{faegh2013self,

title = {A self-sensing piezoelectric microcantilever biosensor for detection of ultrasmall adsorbed masses: theory and experiments},

author = {Samira Faegh and Nader Jalili and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Sensors},

volume = {13},

number = {5},

pages = {6089--6108},

publisher = {Multidisciplinary Digital Publishing Institute},

abstract = {Detection of ultrasmall masses such as proteins and pathogens has been made possible as a result of advancements in nanotechnology. Development of label-free and highly sensitive biosensors has enabled the transduction of molecular recognition into detectable physical quantities. Microcantilever (MC)-based systems have played a widespread role in developing such biosensors. One of the most important drawbacks of all of the available biosensors is that they all come at a very high cost. Moreover, there are certain limitations in the measurement equipments attached to the biosensors which are mostly optical measurement systems. A unique self-sensing detection technique is proposed in this paper in order to address most of the limitations of the current measurement systems. A self-sensing bridge is used to excite piezoelectric MC-based sensor functioning in dynamic mode, which simultaneously measures the system’s response through the self-induced voltage generated in the piezoelectric material. As a result, the need for bulky, expensive read-out equipment is eliminated. A comprehensive mathematical model is presented for the proposed self-sensing detection platform using distributed-parameters system modeling. An adaptation strategy is then implemented in the second part in order to compensate for the time-variation of piezoelectric properties which dynamically improves the behavior of the system. Finally, results are reported from an extensive experimental investigation carried out to prove the capability of the proposed platform. Experimental results verified the proposed mathematical modeling presented in the first part of the study with accuracy of 97.48%. Implementing the adaptation strategy increased the accuracy to 99.82%. These results proved the measurement capability of the proposed self-sensing strategy. It enables development of a cost-effective, sensitive and miniaturized mass sensing platform.

Keywords: microcantilever; biosensor; distributed-parameter modeling; mass detection},

keywords = {Sensors},

pubstate = {published},

tppubtype = {article}

}

@article{chapman2013nanoparticles,

title = {Nanoparticles for cancer imaging: The good, the bad, and the promise},

author = {Sandra Chapman and Marina Dobrovolskaia and Keyvan Farahani and Andrew Goodwin and Amit Joshi and Hakho Lee and Thomas Meade and Martin Pomper and Krzysztof Ptak and Jianghong Rao and others},

year  = {2013},

date = {2013-01-01},

journal = {Nano today},

volume = {8},

number = {5},

pages = {454--460},

publisher = {Elsevier},

abstract = {Recent advances in molecular imaging and nanotechnology are providing new opportunities for biomedical imaging with great promise for the development of novel imaging agents. The unique optical, magnetic, and chemical properties of materials at the scale of nanometers allow the creation of imaging probes with better contrast enhancement, increased sensitivity, controlled biodistribution, better spatial and temporal information, multi-functionality and multi-modal imaging across MRI, PET, SPECT, and ultrasound. These features could ultimately translate to clinical advantages such as earlier detection, real time assessment of disease progression and personalized medicine. However, several years of investigation into the application of these materials to cancer research has revealed challenges that have delayed the successful application of these agents to the field of biomedical imaging. Understanding these challenges is critical to take full advantage of the benefits offered by nano-sized imaging agents. Therefore, this article presents the lessons learned and challenges encountered by a group of leading researchers in this field, and suggests ways forward to develop nanoparticle probes for cancer imaging.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kumar2013third,

title = {Third generation gold nanoplatform optimized for radiation therapy},

author = {Rajiv Kumar and Houari Korideck and Wilfred Ngwa and Ross I Berbeco and Mike G Makrigiorgos and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

journal = {Translational cancer research},

volume = {2},

number = {4},

publisher = {NIH Public Access},

abstract = {We report the design and fabrication of third generation ultrasmall PEGylated gold nanoparticles based platform (AuRad™) optimized for applications in radiation therapy. The AuRad™ nanoplatform has the following key features: (I) surface coating of hetero-bifunctional-PEG with amine, carboxyl, methoxy functional groups, which make this a versatile nanoplatform to conjugate various moieties like fluorophores, peptides, drugs, radiolabels; (II) size that is optimized for longer circulation, higher tumor uptake and modulated clearance; (III) high radiation enhancement. We have synthesized ultrasmall 2–3 nm gold nanoparticles, followed by attachment of hetero-bifunctional PEG and further conjugation of fluorophore AlexaFlour 647 for optical imaging, with a stability of more than 6 months. Confocal bioimaging with HeLa cells showed robust uptake of biocompatible nanoparticles in cells. Irradiation experiments X-rays showed greater than 2.8-fold cell kill enhancement as demonstrated by clonogenic survival assays. The results indicate that AuRad nanoplatform can act as potential theranostic agent in radiation therapy.



Keywords: Gold nanoparticles, PEGylation, multifunctional nanoparticles, clonogenic assay, radiation therapy},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{petrov2013electric,

title = {Electric field encephalography as a tool for functional brain research: a modeling study},

author = {Yury Petrov and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

journal = {PloS one},

volume = {8},

number = {7},

publisher = {Public Library of Science},

abstract = {We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.},

keywords = {Nanomedicine, Neurotechnology},

pubstate = {published},

tppubtype = {article}

}

@article{faegh2013cost,

title = {A cost-effective self-sensing biosensor for detection of biological species at ultralow concentrations},

author = {Samira Faegh and Nader Jalili and Ozgur Yavuzcetin and Dattatri Nagesha and Rajiv Kumar and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

journal = {Journal of Applied Physics},

volume = {113},

number = {22},

pages = {224905},

publisher = {American Institute of Physics},

abstract = {Detection of ultrasmall masses and identification of biological molecules have been made possible as a result of advances in nanotechnology. Development of biosensing tools has significantly contributed to high-throughput diagnosis and analytical sensing exploiting high affinity of biomolecules. MicroCantilever (MC)-based detection has emerged as a promising biosensing tool for offering label-free and cost-effective sensing capabilities. One of the main criteria determining the success of each biosensor is the capability of the sensing platform to operate in aqueous media. Although being characterized with high sensitivity and simplicity, MCs do not provide an effective tool for measurement of marker proteins in liquid media due to large hydrodynamic damping and losses in the surrounding liquid. In this study, we describe two approaches to high sensitivity biomolecular detection using piezoelectric microcantilevers. (i) Immobilized Mass Detection in Air using electro-mechanical resonance: a unique self-sensing measurement technique is reported utilizing a self-sensing circuit consisting of a piezoelectric MC to address the mentioned limitation. The capability of the self-sensing measurement technique was first verified by detecting ultrasmall biological masses immobilized over the surface of MC by monitoring the shift in fundamental mechanical resonance frequency of the system in air and comparing it with optical-based measurement. This was further utilized for calibration of mass detection in liquid media. (ii) Immobilized Mass Detection in Liquid using the electrical self-sensing circuit's resonance: Once the capability to detect adsorbed mass was verified, the self-sensing platform was implemented to detect different concentrations of target molecule (glucose in this study) in liquid media by adopting the highly sensitive resonance frequency of the whole circuit instead of the mechanical response of MC. Molecular binding occurring over the surface of MC changes the capacitance of the total interface thus changing the resonance frequency of the circuit. The amount of shift in the measured circuit's resonance frequency provides qualitative and quantitative insight into the amount of target protein concentration. The reported diagnostic platform offers a simple, cost-effective, all-electronics method of detection where the need for any bulky, expensive optical based measurement is eliminated. Utilizing this technique, physiological concentration of glucose as low as 500 nM was measured in liquid media. This sensitivity is significantly higher than what has been previously reported using other mechanical resonance techniques.},

keywords = {Sensors},

pubstate = {published},

tppubtype = {article}

}

@article{ngwa2013toward,

title = {Toward Customizable Radiation Therapy Enhancement (CuRE) With Gold Nanoparticles Released, In Situ, From Gold-Loaded Brachytherapy Spacers},

author = {W Ngwa and H Korideck and R Kumar and S Sridhar and K David and N Paul and R Berbeco and R Cormack and G Makrigiorgos},

year  = {2013},

date = {2013-01-01},

journal = {International Journal of Radiation Oncology• Biology• Physics},

volume = {87},

number = {2},

pages = {S151},

publisher = {Elsevier},

abstract = {Purpose/Objective(s)

Loading routinely used brachytherapy spacers with non-toxic/biocompatible gold nanoparticles (AuNP), which can be released in situ to serve as radiosensitizers is a novel potential strategy for prostate tumor sub-volume boosting or dose-painting. This study investigates the release and diffusion of the AuNP from the brachytherapy spacer in vivo using CT imaging.

Materials/Methods

Gold-loaded brachytherapy spacers (GBS) (ca. 0.8 mm x 5 mm) were produced using AuNP and biodegradable PLGA copolymer. The GBS was implanted in mice using a brachytherapy needle and CBCT-imaged over time using the small animal radiation research platform (SARRP). The CT images were exported to imageJ and the intensity of the implanted spacer evaluated at different time points. Also, to simulate a burst release of the AuNP from an implanted spacer, 20 mg Au/mL concentration of 15 nm polymer coated AuNP suspended in 20 μL phosphate-buffered saline at pH 7.4, was injected intratumorally, and the AuNP diffusion monitored via serial CT imaging over 5 time points in hours: 0.5, 48, 120, 144, and 160. The CT images were then exported to imageJ and the pixel intensities for 5 sample tumor regions of interest (at: left, right, center, anterior, posterior) extracted to assess AuNP diffusion.

Results

Results for the implanted GBS showed that the CT intensity of the spacer decreased over time, indicating the release of the AuNP as the PLGA degrades in vivo. Meanwhile, the CBCT images from the AuNP burst release study showed clear evidence of AuNP diffusion. For example, at the site of AuNP release, the CT image intensity decreased by over 160% during the investigated time range (0.5 h – 160 h). During the same time, the intensity in the tumor subvolume or ROI on the opposite side of the release site increased by over 140%. The diffusion results also showed that for the 15 nm AuNP size, potent AuNP concentrations can reside within the tumor sub-volume for a sustained period of time.

Conclusions

The results provide the first in vivo evidence of AuNP release from gold loaded brachytherapy spacers. The sustained residence of potent AuNP concentrations in the tumor sub-volume could allow for significant dose boosting during brachytherapy. Such boosting could be further customized (e.g., by varying AuNP size, functionalization, spacer degradation time, etc.) since the intra-tumor biodistribution depends on such parameters. Overall, the results provide a useful basis for future R&D towards the development of Customizable Radiation therapy Enhancement (CuRE) with AuNP for prostate cancer. Potential clinical applications for such a new approach are anticipated in salvage brachytherapy, and sub-volume radiation boosting during initial treatment to help prevent prostate cancer recurrence.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kumar2013facile,

title = {Facile synthesis of PEGylated PLGA nanoparticles encapsulating doxorubicin and its in vitro evaluation as potent drug delivery vehicle},

author = {Rajiv Kumar and Apurva Kulkarni and Jude Nabulsi and Dattatri K Nagesha and Robert Cormack and Mike G Makrigiorgos and Srinivas Sridhar},

year  = {2013},

date = {2013-01-01},

journal = {Drug delivery and translational research},

volume = {3},

number = {4},

pages = {299--308},

publisher = {Springer US},

abstract = {The advent of nanotechnology has bolstered a variety of nanoparticle-based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle’s physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy. The simple nanoprecipitation method reported here resulted in very robust PEGylated PLGA nanoparticles with close to 95 % drug encapsulation efficiency. The nanoparticles showed a size of ~110 nm as characterized by TEM and DLS. The nanoparticles were further characterized by optical UV–Visible and fluorescence spectroscopy. The encapsulated doxorubicin showed a sustained release (>80 %) from the nanoparticles matrix over a period of 8 days. The drug delivery efficiency of the nanoparticles was confirmed in vitro confocal imaging with PC3 and HeLa cell lines. In vitro quantitative estimation of drug accumulation in PC3 cell line showed a 22 times higher concentration of drug in case of nanoparticle-based formulation in comparison to free drug and this was further reflected in the in vitro cytotoxicity assays. Overall the synthesis method reported here provides a simple and robust PLGA-based platform for efficient drug delivery and imaging of cancer cells in vitro and in vivo.



},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{andersonour,

title = {Our thanks to all those who have helped with this issue of Nanomedicine. Listed below are authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication.},

author = {D Anderson and A Archakov and K Avgoustakis and A Baumgartner and R Bawa and M Bernardo and V Biricova and R Brayner and MW Brechbiel and J Buse and others},

year  = {2012},

date = {2012-12-20},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kumar2012vitro,

title = {In vitro evaluation of theranostic polymeric micelles for imaging and drug delivery in cancer},

author = {Rajiv Kumar and Apurva Kulkarni and Dattatri K Nagesha and Srinivas Sridhar},

year  = {2012},

date = {2012-01-01},

journal = {Theranostics},

volume = {2},

number = {7},

pages = {714},

publisher = {Ivyspring International Publisher},

abstract = {We describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.



For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of <50 nm for the micellar formulations with very narrow size distribution. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.



Keywords: Theranostic Polymeric Micelles, Imaging, Drug Delivery, Cancer

},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{berbeco2012dna,

title = {DNA damage enhancement from gold nanoparticles for clinical MV photon beams},

author = {Ross I Berbeco and Houari Korideck and Wilfred Ngwa and Rajiv Kumar and Janki Patel and Srinivas Sridhar and Sarah Johnson and Brendan D Price and Alec Kimmelman and Mike G Makrigiorgos},

year  = {2012},

date = {2012-01-01},

journal = {Radiation research},

volume = {178},

number = {6},

pages = {604--608},

publisher = {The Radiation Research Society},

abstract = {OTHER| NOVEMBER 13 2012

DNA Damage Enhancement from Gold Nanoparticles for Clinical MV Photon Beams 

Ross I. Berbeco; Houari Korideck; Wilfred Ngwa; Rajiv Kumar; Janki Patel; Srinivas Sridhar; Sarah Johnson; Brendan D. Price; Alec Kimmelman; G. Mike Makrigiorgos

Radiat Res (2012) 178 (6): 604–608.

https://doi.org/10.1667/RR3001.1

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In this study, we quantify the relative damage enhancement due to the presence of gold nanoparticles (GNP) in vitro in a clinical 6 MV beam for various delivery parameters and depths. It is expected that depths and delivery modes that produce a larger proportions of low-energy photons will have a larger effect on the cell samples containing GNP. HeLa cells with and without 50 nm GNP were irradiated at depths of 1.5, 5, 10, 15 and 20 cm. Conventional beams with square aperture sizes 5, 10 and 15 cm at isocenter, and flattening filter free (FFF) beams were used. Relative DNA damage enhancement with GNP was evaluated by γ-H2AX staining. Statistically significant increases in DNA damage with GNP, compared to the absence of GNP, were observed for all depths and delivery modes. Relative to the shallowest depth, damage enhancement was observed to increase as a function of increasing depth for all deliveries. For the conventional (open field) delivery, DNA damage enhancement with GNP was seen to increase as a function of field size. For FFF delivery, a substantial increase in enhancement was found relative to the conventional field delivery. The measured relative DNA damage enhancement validates the theoretically predicted trends as a function of depth and delivery mode for clinical MV photon beams. The results of this study open new possibilities for the clinical development of gold nanoparticle-aided radiation therapy.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{yavuzcetin2012photonic,

title = {Photonic crystal fabrication in lithium niobate via pattern transfer through wet and dry etched chromium mask},

author = {Ozgur Yavuzcetin and Herman P Novikov and Rebecca L Dally and Sean T Malley and Nicholas R Perry and Birol Ozturk and Srinivas Sridhar},

year  = {2012},

date = {2012-01-01},

journal = {Journal of Applied Physics},

volume = {112},

number = {7},

pages = {074303},

publisher = {American Institute of Physics},

abstract = {The need to fabricate photonic crystals from lithium niobate (LN) with accurate feature sizes is important to the development of optoelectronic devices. This paper reports a fabrication process to dry etch X-cut LN at a submicron scale using electron beam lithography and chromium as a hard mask. The chromium mask was used for both dry-etching and wet-etching in a unique method. Problems and solutions found during fabrication are presented. Arrays consisting of 400 nm diameter holes with a high aspect ratio were etched in LN, creating photonic crystals modeled to transmit light in the infrared spectrum.},

keywords = {Sensors},

pubstate = {published},

tppubtype = {article}

}

@article{berbeco2012tu,

title = {TU-C-BRB-11: In Vitro Dose Enhancement from Gold Nanoparticles under Different Clinical MV Photon Beam Configurations},

author = {R Berbeco and H Korideck and W Ngwa and R Kumar and J Patel and S Sridhar and S Johnson and B Price and A Kimmelman and M Makrigiorgos},

year  = {2012},

date = {2012-01-01},

journal = {Medical Physics},

volume = {39},

number = {6Part23},

pages = {3900--3901},

publisher = {American Association of Physicists in Medicine},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{ngwa2012vitro,

title = {In vitro dose enhancement from gold nanoparticles during low-dose-rate gamma irradiation with I-125 brachytherapy seeds},

author = {W Ngwa and H Korideck and A Kimmelman and AI Kassis and R Kumar and S Sridhar and M Makrigiorgos and RA Cormack},

year  = {2012},

date = {2012-01-01},

journal = {International Journal of Radiation Oncology• Biology• Physics},

volume = {84},

number = {3},

pages = {S134},

publisher = {Elsevier},

abstract = {Purpose/Objective(s)

Recent studies have predicted substantial dose enhancement to tumors when gold nanoparticles (AuNP) are employed as adjuvants to radiation therapy at kV energies. Because the enhancement results from processes at kV energies, some studies proposed gold nanoparticle-aided brachytherapy as a radiation therapy approach with potential to meet technical and clinical requirements for implementation. To the best of our knowledge, there has been no study providing clear experimental evidence to corroborate the substantial dose enhancement predictions when irradiating with low dose rate gamma photons from brachytherapy sources. This study investigates the in vitro dose enhancement of AuNP during irradiation of cancer cells by I-125 low dose rate brachytherapy sources.

Materials/Methods

HeLa cell cultures were incubated with and without gold nanoparticles (AuNP) in alternate wells of an 8 well-chamber slide; 4 wells on each slide had cell cultures with AuNP while 4 wells contained cell cultures with no AuNP. Two slides were prepared for each experiment: one slide to be irradiated while the other serves as sham-irradiation control. The cells were irradiated with gamma photons from I-125 brachytherapy seeds in a plaque contained in a custom-built irradiation jig. The plaque was designed to achieve a relatively homogeneous dose distribution in the plane of the cell culture slide. Four sets of irradiation experiments were conducted at 370C at dose rates ranging from 2.1 cGy/hr to 4.5 cGy/hr. The dose rates were varied by varying the height of the cell culture slide above the plaque containing the I-125 seeds. Residual gammaH2AX was measured 24 hours after irradiation and used to compare the dose response of the cells with and without AuNP. In addition, the relative dose enhancement factor (DEF), representing the ratio of the dose to the cells with and without the presence of AuNP, was estimated from the data.

Results

From the dose response behavior, the results show that the biologic effect when irradiating with 0.2 mg/mL concentration of AuNP is up to 2.3 times greater than without AuNP. This major increase in radiation damage to cancer cells incubated with AuNP corresponds to an estimated DEF of over 3.5.

Conclusions

Our findings provide the first experimental evidence of substantial dose enhancement from gold nanoparticles during low dose rate gamma irradiation from brachytherapy sources. These in vitro study results provide impetus for further preclinical and clinical investigations in the development of gold nanoparticle-aided brachytherapy.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cormack2012locally,

title = {Locally Drug Enhanced Brachytherapy: A Comparison of 2 Approaches Based on Biologically Effective Dose},

author = {R Cormack and P Nguyen and AV D'Amico and S Sridhar and GM Makrigiorgos},

year  = {2012},

date = {2012-01-01},

journal = {International Journal of Radiation Oncology• Biology• Physics},

volume = {84},

number = {3},

pages = {S854--S855},

publisher = {Elsevier},

abstract = {Purpose/Objective(s)

Permanent prostate brachytherapy may be enhanced by delivering radiosensitizer to the target during the implant process. Nanoparticles released from a substrate can deliver drug over an extended period of time and can be engineered to adjust their diffusion parameters. Nanoparticle eluting polymers have been proposed to coat radioactive sources or to form brachytherapy spacers as a way of delivering drug to the prostate. This work determines whether it is preferable to deliver radiosensitizer from sources or spacers.

Materials/Methods

The relative effectiveness of spacers or sources as sources of sensitizer was evaluated by comparing biologic effective dose (BED) of the combined effect of radiation and drug distributions within the prostate. Treatment plans of six patients receiving 125I prostate implants were analyzed under an IRB approved protocol. Target contours were extracted as were the locations of radioactive sources and spacers. Radiation dose was calculated according to AAPM TG43 methodology. Drug distributions were calculated from a solution of the diffusion equation, relative to the steady state concentration at the eluter's surface, for a range of diffusion-elimination modulus (φb) values and concentration needed for maximum sensitization (Cs). φb is viewed as a variable because the properties of the nanoparticles can be adjusted to affect diffusion and time of residence. Cs is treated as a variable because the amplitude of the drug distribution depends on the capacity of the implanted object and the time frame of release. BED calculations of the composite effect were done. The calculations were compared to an approach where the location of the spacers was allowed to be adjusted.

Results

The ratio of the BED for the two delivery approaches is presented in the 2D parameter space of φb and Cs. A full sensitization region, corresponding to low values of φb and Cs, shows no difference between approaches. The majority of the remaining parameter space, showed that using spacers to radiosensitize results in a greater BED. Changing the spacer locations from fixed by the treatment plan to adjustable allowed further increase of BED.

Conclusions

Using brachytherapy spacers as a vehicle to deliver radiosensitizing nanoparticles offers a greater potential to increase the effectiveness of prostate brachytherapy by in-situ radiosensitization. Further increase was achieved by treating spacer location as planning parameter. Using implanted non-radioactive devices for local radiosensitization suggests the potential of planned chemical distributions in conjunction with radiation planning to produce an optimal combined result.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{H.Lewisa2011,

title = {Thermomagnetic determination of Fe3O4 magnetic nanoparticle diameters for biomedical applications},

author = {Brian D.Plouffea and Dattatri K.Nagesha and Robert S.DiPietro and Srinvas Sridhar and Don Heimand and Shashi K.Murthya and Lewis H.Lewisa

},

doi = {S0304885311002423},

year  = {2011},

date = {2011-09-01},

journal = {Journal of Magnetism and Magnetic Materials},

volume = {323},

number = {17},

pages = {2310-2317},

abstract = {The utility and promise of magnetic nanoparticles (MagNPs) for biomedicine rely heavily on accurate determination of the particle diameter attributes. While the average functional size and size distribution of the magnetic nanoparticles directly impact the implementation and optimization of nanobiotechnology applications in which they are employed, the determination of these attributes using electron microscopy techniques can be time-consuming and misrepresentative of the full nanoparticle population. In this work the average particle diameter and distribution of an ensemble of Fe3O4 ferrimagnetic nanoparticles are determined solely from temperature-dependent magnetization measurements; the results compare favorably to those obtained from extensive electron microscopy observations. The attributes of a population of biocompatible Fe3O4 nanoparticles synthesized by a thermal decomposition method are obtained from quantitative evaluation of a model that incorporates the distribution of superparamagnetic blocking temperatures represented through thermomagnetization data. The average size and size distributions are determined from magnetization data via temperature-dependent zero-field-cooled magnetization. The current work is unique from existing approaches based on magnetic measurement for the characterization of a nanoparticle ensemble as it provides both the average particle size as well as the particle size distribution.



},

keywords = {featured, Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{Makrigiorgos2011,

title = {Optimal drug release schedule for in-situ radiosensitization of image guided permanent prostate implants},

author = {Robert A. Cormack; Paul L. Nguyen; Anthony V. D'Amico; Sri Sridhar; Mike Makrigiorgos

},

doi = {10.1117/12.878139},

year  = {2011},

date = {2011-03-03},

journal = {Proceedings Volume 7964, Medical Imaging 2011: Visualization, Image-Guided Procedures, and Modeling},

volume = {7964},

number = {2011},

abstract = {Planned in-situ radiosensitization may improve the therapeutic ratio of image guided 125I prostate brachytherapy. Spacers used in permanent implants may be manufactured from a radiosensitizer-releasing polymer to deliver protracted localized sensitization of the prostate. Such devices will have a limited drug-loading capacity, and the drug release schedule that optimizes outcome, under such a constraint, is not known. This work determines the optimal elution schedules for 125I prostate brachytherapy. The interaction between brachytherapy dose distributions and drug distribution around drug eluting spacers is modeled using a linear-quadratic (LQ) model of cell kill. Clinical brachytherapy plans were used to calculate the biologic effective dose (BED) for planned radiation dose distributions while adding the spatial distributions of radiosensitizer while varying the temporal release schedule subject to a constraint on the drug capacity of the eluting spacers. Results: The greatest increase in BED is achieved by schedules with the greatest sensitization early in the implant. Making brachytherapy spacers from radiosensitizer eluting polymer transforms inert parts of the implant process into a means of enhancing the effect of the brachytherapy radiation. Such an approach may increase the therapeutic ratio of prostate brachytherapy or offer a means of locally boosting the radiation effect without increasing the radiation dose to surrounding tissues.

},

keywords = {featured, Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{savo2011observation,

title = {Observation of slow-light in a metamaterials waveguide at microwave frequencies},

author = {Salvatore Savo and BDF Casse and Wentao Lu and Srinivas Sridhar},

year  = {2011},

date = {2011-01-01},

journal = {Applied Physics Letters},

volume = {98},

number = {17},

pages = {171907},

publisher = {American Institute of Physics},

abstract = {We report an experimental observation of slow-light in the GHz microwave regime utilizing the mechanism of the degeneracy of forward and backward waves in a planar waveguide consisting of a dielectric core cladded by single-negative metamaterial.



},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}

@article{ye2011tuning,

title = {Tuning the optical properties of metamaterials based on gold nanowire arrays embedded in alumina},

author = {Yong-Hong Ye and YJ Huang and WT Lu and BDF Casse and D Xiao and SP Bennett and D Heiman and L Menon and S Sridhar},

year  = {2011},

date = {2011-01-01},

journal = {Optical Materials},

volume = {33},

number = {11},

pages = {1667--1670},

publisher = {North-Holland},

abstract = {We fabricated a series of gold nanowires/alumina composite films with different wire lengths. Optical transmission measurements confirmed that the composite films exhibit transverse and longitudinal surface plasmon resonances. We show that the wavelength of the longitudinal resonance is sensitive to nanowire length, while that of the transverse resonance is not. The experimental results are in agreement with the modeled results based on the Maxwell Garnett effective medium theory. Moreover, the window for negative refraction of the samples can be tuned in synchronism with the longitudinal resonance by the nanowire length.},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}

@article{yavuzcetin2011conicity,

title = {Conicity and depth effects on the optical transmission of lithium niobate photonic crystals patterned by focused ion beam},

author = {Ozgur Yavuzcetin and Birol Ozturk and Dong Xiao and Srinivas Sridhar},

year  = {2011},

date = {2011-01-01},

journal = {Optical Materials Express},

volume = {1},

number = {7},

pages = {1262--1271},

publisher = {Optical Society of America},

abstract = {We report on novel focused ion beam fabrication techniques that can greatly improve the optical performance of photonic crystal structures. The finite depth and conicity effects of holes and trenches in Lithium Niobate (LN) photonic crystals have been theoretically analyzed, showing that the conicity causes refraction into the bulk sample, resulting in high transmission loss and no useful spectral features. The techniques for reducing the conicity angle from 25° to 5° were explained for the focused ion beam (FIB) milled structures.



©2011 Optical Society of America},

keywords = {Sensors},

pubstate = {published},

tppubtype = {article}

}

@article{casse2011robust,

title = {Robust method to determine the resolution of a superlens by analyzing the near-field image of a two-slit object},

author = {BDF Casse and WT Lu and YJ Huang and S Sridhar},

year  = {2011},

date = {2011-01-01},

journal = {arXiv preprint arXiv:1105.0182},

abstract = {In the last decade, metamaterials-based superlenses, with a resolution below Abbe's diffraction limit, have emerged. To obtain a rough estimate of the resolution of such superlenses, imaging of two subwavelength slits, separated by a subwavelength gap textit{d} is typically performed. The resolution Δ of the lens corresponds to the minimum possible gap dmin for which a distinct image of the two slits can be resolved (Δ∼dmin). In this letter, we present a more quantitative estimate of the resolution of manufactured lenses by fitting analytical near-field image profiles, obtained from imaging a two-slit object with a theoretical negative-index lens of known resolution, to experimental data. We conclude the discussion by applying our analytical method to 3 case examples of superlensing from the literature. As shown, this method is particularly attractive for rapidly assessing the performance of fabricated superresolution lenses.},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}

@article{cassesuperresolution,

title = {Superresolution imaging and superfocusing with negative-index metamaterials},

author = {Bernard Didier F Casse and Srinivas Sridhar},

year  = {2010},

date = {2010-03-19},

abstract = {Developments in higher-resolution optics have often led to rapid scientific and technological progress in the life sciences and engineering. In 1873, Ernst Abbe showed1 that the spatial resolution of optical-imaging instruments is limited by diffraction because of the finite wavelength of light. Abbe’s diffraction-limit theory implies that the resolving power of optical components cannot be smaller than half the wavelength of the incident light. Nanoscale optical elements that can mold the flow of light offer the potential of entirely new modalities of superresolution imaging. With a vision to build superlenses capable of resolving subwavelength details, in the last decade the photonics community has focused on fabricating tiny metallic inclusions (or, closely related, plasmonic architectures) characterized by a negative index of refraction. 2 Unfortunately, such metamaterials suffer from material losses enhanced by resonances, leading to a degradation of functionality. Instead, our group has demonstrated successful performance of highly functional nanostructured metamaterials in ‘low-loss’ dielectric platforms such as metal-dielectric composites and III-V semiconductors (composed of indium phosphide/indium gallium arsenide phosphide: InP/InGaAsP). We recently reported the experimental realization of superresolution imaging with a low-loss 3D nanolens, 3 comprised of gold nanowires embedded in nanoporous alumina: see Figure 1 (right). This 3D nanolens, manufactured using a combination of bottom-up self-assembly and electrochemical process, transmits subwavelength details down to= 4 (: Wavelength) and over a significant distance of more than …},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}

@article{gultepe2010nanoporous,

title = {Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices},

author = {Evin Gultepe and Dattatri Nagesha and Srinivas Sridhar and Mansoor Amiji},

year  = {2010},

date = {2010-01-01},

journal = {Advanced drug delivery reviews},

volume = {62},

number = {3},

pages = {305--315},

publisher = {Elsevier},

abstract = {The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al2O3), titanium oxide (TiO2) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution pro?les of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release pro?les extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved ef?cacy and integration of implants in a variety of therapeutic situations.



},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{casse2010super,

title = {Super-resolution imaging using a three-dimensional metamaterials nanolens},

author = {BDF Casse and WT Lu and YJ Huang and E Gultepe and L Menon and S Sridhar},

year  = {2010},

date = {2010-01-01},

journal = {Applied Physics Letters},

volume = {96},

number = {2},

pages = {023114},

publisher = {American Institute of Physics},

abstract = {Super-resolution imaging beyond Abbe’s diffraction limit can be achieved by utilizing an optical medium or “metamaterial” that can either amplify or transport the decaying near-field evanescent waves that carry subwavelength features of objects. Earlier approaches at optical frequencies mostly utilized the amplification of evanescent waves in thin metallic films or metal-dielectric multilayers, but were restricted to very small thicknesses (⪡λ, wavelength) and accordingly short object-image distances, due to losses in the material. Here, we present an experimental demonstration of super-resolution imaging by a low-loss three-dimensional metamaterial nanolens consisting of aligned gold nanowires embedded in a porous alumina matrix. This composite medium possesses strongly anisotropic optical properties with negative permittivity in the nanowire axis direction, which enables the transport of both far-field and near-field components with low-loss over significant distances (>6λ), and over a broad spectral range. We demonstrate the imaging of large objects, having subwavelength features, with a resolution of at least λ/4 at near-infrared wavelengths. The results are in good agreement with a theoretical model of wave propagation in anisotropic media.

The authors would like to thank M. G. Silveirinha, D. Heiman, J. Sokoloff, and F. Camino for useful discussions and comments. This work was financially supported by the Air Force Research Laboratories, Hanscom through Grant No. FA8718-06-C-0045 and NSF through Grant No. PHY-0457002. The work was also performed in part at the Kostas Center at Northeastern University and the Center for Nanoscale Systems, a member of NNIN, which is supported by the National Science Foundation under NSF Award No. ECS-0335765. Research carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886.},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}

@article{stambaugh2010we,

title = {WE-E-204B-02: Release Kinetics of Radio-Sensitizers from Nanoporous Coatings on Gold Fiducials: Biological In-Situ Dose-Painting for IGRT},

author = {C Stambaugh and D Tada and D Nagesha and E Jost and C Levy and RA Cormack and M Makrigiorgos and S Sridhar},

year  = {2010},

date = {2010-01-01},

journal = {Medical Physics},

volume = {37},

number = {6Part13},

pages = {3437--3438},

publisher = {American Association of Physicists in Medicine},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cormack2010drug,

title = {Drug Eluting Brachytherapy Spacers: A Potential for Biologically-Enhanced Brachytherapy},

author = {Robert A Cormack and Dattatri Nagesha and Evin Gultepe and Paul Nguyen and Anthony V D'Amico and Srinivas Sridhar and Mike Makrigiorgos},

year  = {2010},

date = {2010-01-01},

journal = {Brachytherapy},

volume = {9},

pages = {S48--S49},

publisher = {Elsevier},

abstract = {Purpose: Ultrasound-guided prostate brachytherapy routinely implants spacers between the 125I radiation sources, that provide no therapeutic benefit although they are essential to the technical completion of the implant. The spacers offer a vehicle for in-situ delivery of radio-sensitizer, or other agents, which could increase the biologic effective dose of the radiation. This work studies the achievable drug coverage as a function of the chemical and physical properties of the drugs and devices.

Materials and Methods: Fluorescent doxorubicin in a polymer suspension and gold substrate were used to evaluate the ability to create a radio-opaque drug eluter. Elution kinetics from polymer coating of gold substrate was measured via fluorescence spectrometry. An analytic solution to the diffusion elimination equation was used to perform computer modeling of drug distributions produced by configurations of eluters placed within ultrasound guided prostate implants. Measures of tumor coverage and normal tissue involvement are evaluated for multiple combinations of eluter sizes and diffusion elimination moduli φb.

Results: Timed-release of doxorubicin from a polymer coating on a gold substrate, as shown in the top half of the figure, is technically possible. The many spacers used in prostate brachytherapy are sufficient to sensitize a portion of the prostate with values of φb close to the calculated ones. The use of drug-eluting brachytherapy spacers would enable a more localized enhancement in biologic effective dose than what can be delivered by a local brachytherapy boost. The bottom half of the figure shows a prostate implant at treated at our institution and and how it could be locally enhanced with the addition of a small number of drug eluting spacers.

Conclusions: IGRT techniques, such as ultrasound-guided brachytherapy, already implant devices within tumors as part of the standard of care. These devices may be enhanced with drug-eluting coatings to provide an in-situ increase in biologic effective dose without increasing the physical dose involved in the therapy. Generalization of this biologically in-situ enhanced IGRT (BIS-IGRT) to other agents in combination with advances in biologic imaging may provide an opportunity for personalized biologically in-situ enhanced brachytherapy.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{lu2010storing,

title = {Storing light in active optical waveguides with single-negative materials},

author = {WT Lu and YJ Huang and BDF Casse and RK Banyal and S Sridhar},

year  = {2010},

date = {2010-01-01},

journal = {Applied Physics Letters},

volume = {96},

number = {21},

pages = {211112},

publisher = {American Institute of Physics},

abstract = {We show that a nonresonant planar waveguide consisting of conventional dielectric cladded with single-negative materials supports degenerate propagating modes for which the group velocity and total energy flow can be zero if the media are lossless. Absorptive losses will destroy the zero-group velocity condition for real frequency/complex wave vector modes.



},

keywords = {Metamaterials and Nanophotonics},

pubstate = {published},

tppubtype = {article}

}