@article{yang2023sustained,

title = {Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer},

author = {Shicheng Yang and Allen Green and Needa Brown and Alexis Robinson and Merline Senat and Bryanna Testino and Daniela M Dinulescu and Srinivas Sridhar},

year  = {2023},

date = {2023-01-01},

journal = {Frontiers in Oncology},

volume = {13},

pages = {1175617},

publisher = {Frontiers},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{thong2022multifunctional,

title = {Multifunctional nanocarriers of Fe3O4@ PLA-PEG/curcumin for MRI, magnetic hyperthermia and drug delivery},

author = {Phan Quoc Thong and Le Thi Thu Huong and Nguyen Dac Tu and Hoang Thi My Nhung and Lam Khanh and Do Hung Manh and Pham Hong Nam and Nguyen Xuan Phuc and Javier Alonso and Ju Qiao and others},

year  = {2022},

date = {2022-01-01},

journal = {Nanomedicine},

number = {0},

publisher = {Future Medicine Ltd London, UK},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{rodell2021quantification,

title = {Quantification of cellular drug biodistribution addresses challenges in evaluating in vitro and in vivo encapsulated drug delivery},

author = {Christopher B Rodell and Paige Baldwin and Bianca Fernandez and Ralph Weissleder and Srinivas Sridhar and John Matthew Dubach},

year  = {2021},

date = {2021-01-01},

journal = {Advanced therapeutics},

volume = {4},

number = {3},

pages = {2000125},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{zhang2021sustained,

title = {Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in BRCA1-deficient mice},

author = {Di Zhang and Bijay Singh and Jessica Moerland and Owen Mitchell and Lizbeth Lockwood and Sarah Carapellucci and Srinivas Sridhar and Karen T Liby},

year  = {2021},

date = {2021-01-01},

journal = {Scientific Reports},

volume = {11},

number = {1},

pages = {1234},

publisher = {Nature Publishing Group UK London},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{yang2021recent,

title = {Recent developments in nanomedicine for pediatric cancer},

author = {Shicheng Yang and Mia Wallach and Apurva Krishna and Raushan Kurmasheva and Srinivas Sridhar},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Clinical Medicine},

volume = {10},

number = {7},

pages = {1437},

publisher = {MDPI},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cheng2020targeted,

title = {Targeted Intravenous Nanoparticle Delivery: Role of Flow and Endothelial Glycocalyx Integrity},

author = {Ming J Cheng and Ronodeep Mitra and Chinedu C Okorafor and Alina A Nersesyan and Ian C Harding and Nandita N Bal and Rajiv Kumar and Hanjoong Jo and Srinivas Sridhar and Eno E Ebong},

year  = {2020},

date = {2020-01-01},

journal = {Annals of Biomedical Engineering},

pages = {1--14},

abstract = {Therapies for atherosclerotic cardiovascular disease should target early disease stages and specific vascular sites where disease occurs. Endothelial glycocalyx (GCX) degradation compromises endothelial barrier function and increases vascular permeability. This initiates pro-atherosclerotic lipids and inflammatory cells to penetrate vessel walls, and at the same time this can be leveraged for targeted drug delivery. In prior cell culture studies, GCX degradation significantly increased endothelial cell uptake of nanoparticle vehicles that are designed for drug delivery, compared to the effects of intact GCX. The present study assessed if the cell culture findings translate to selective nanoparticle uptake in animal vessels. In mice, the left carotid artery (LCA) was partially ligated to disturb blood flow, which induces GCX degradation, endothelial dysfunction, and atherosclerosis. After ligation, the LCA vessel wall exhibited.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{mitra2020high,

title = {High fat diet versus disturbed blood flow conditions: Implications for endothelial glycocalyx integrity and pre-atherosclerotic inflammation},

author = {Ronodeep Mitra and Ju Qiao and Sudharsan Madhavan and Gerard O’Neil and Bailey Ritchie and Praveen Kulkarni and Srinivas Sridhar and Anne Ven and Erica Cherry and Craig Ferris and others},

year  = {2020},

date = {2020-01-01},

journal = {The FASEB Journal},

volume = {34},

number = {S1},

pages = {1–1},

publisher = {The Federation of American Societies for Experimental Biology},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{schuemann2020roadmap,

title = {Roadmap for metal nanoparticles in radiation therapy: Current status, translational challenges, and future directions},

author = {Jan Schuemann and Alexander F Bagley and Ross Berbeco and Kyle Bromma and Karl T Butterworth and Hilary L Byrne and B Devika Chithrani and Sang Hyun Cho and Jason R Cook and Vincent Favaudon and others},

year  = {2020},

date = {2020-01-01},

journal = {Physics in Medicine & Biology},

volume = {65},

number = {21},

pages = {21RM02},

publisher = {IOP Publishing},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{virani2020noninvasive,

title = {Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption},

author = {Needa A Virani and Olivia J Kelada and Sijumon Kunjachan and Alexandre Detappe and Jihun Kwon and Jennifer Hayashi and Ana Vazquez-Pagan and Douglas E Biancur and Thomas Ireland and Rajiv Kumar and others},

year  = {2020},

date = {2020-01-01},

journal = {Plos one},

volume = {15},

number = {7},

pages = {e0236245},

publisher = {Public Library of Science San Francisco, CA USA},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{mueller2020increased,

title = {Increased carcinoembryonic antigen expression on the surface of lung cancer cells using gold nanoparticles during radiotherapy},

author = {Romy Mueller and Sayeda Yasmin-Karim and Kaylie DeCosmo and Ana Vazquez-Pagan and Srinivas Sridhar and David Kozono and Juergen Hesser and Wilfred Ngwa},

year  = {2020},

date = {2020-01-01},

journal = {Physica Medica},

volume = {76},

pages = {236–242},

publisher = {Elsevier},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{zhang2020localized,

title = {Localized delivery of the PARP inhibitor Talazoparib for chemoprevention of breast cancer},

author = {Di Zhang and Bijay Singh and Jessica Moerland and Owen Mitchell and Lizbeth Lockwood and Sarah Carapellucci and Srinivas Sridhar and Karen Liby},

year  = {2020},

date = {2020-01-01},

journal = {Cancer Research},

volume = {80},

number = {16_Supplement},

pages = {12–12},

publisher = {The American Association for Cancer Research},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kunjachan2020author,

title = {Author correction: Selective priming of tumor Blood Vessels by Radiation therapy enhances nanodrug Delivery},

author = {Sijumon Kunjachan and Shady Kotb and Robert Pola and Michal Pechar and Rajiv Kumar and Bijay Singh and Felix Gremse and Reza Taleeli and Florian Trichard and Vincent Motto-Ros and others},

year  = {2020},

date = {2020-01-01},

journal = {Scientific Reports},

volume = {10},

number = {1},

pages = {15344},

publisher = {Nature Publishing Group UK London},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{singh2020nanoparticle,

title = {Nanoparticle formulations of poly (ADP-ribose) polymerase inhibitors for cancer therapy},

author = {Bijay Singh and Shicheng Yang and Apurva Krishna and Srinivas Sridhar},

year  = {2020},

date = {2020-01-01},

journal = {Frontiers in Chemistry},

volume = {8},

pages = {594619},

publisher = {Frontiers Media SA},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cheng2020targetedb,

title = {Targeted intravenous nanoparticle delivery: role of flow and endothelial glycocalyx integrity},

author = {Ming J Cheng and Ronodeep Mitra and Chinedu C Okorafor and Alina A Nersesyan and Ian C Harding and Nandita N Bal and Rajiv Kumar and Hanjoong Jo and Srinivas Sridhar and Eno E Ebong},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Annals of biomedical engineering},

volume = {48},

pages = {1941–1954},

publisher = {Springer International Publishing},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cheng2019ultrasmall,

title = {Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells},

author = {Ming J Cheng and Nandita N Bal and Priya Prabakaran and Rajiv Kumar and Thomas J Webster and Srinivas Sridhar and Eno E Ebong},

year  = {2019},

date = {2019-01-01},

journal = {International journal of nanomedicine},

volume = {14},

pages = {319},

publisher = {Dove Press},

abstract = {Clinical data show shed endothelial glycocalyx (GCX) components in blood samples of atherosclerotic patients, linking atherosclerotic development to endothelial GCX integrity. Healthy GCX has pores no> 7 nm, and shed GCX has even larger pores. Therefore, we suggest targeting and treating atherosclerosis-prone blood vessels by using nanoscale vehicles to deliver drugs via the nanoscale GCX as it becomes dysfunctional.

Materials and methods

To test our idea, we investigated permeability of nanoparticles in endothelium, as related to a GCX expression. The present work involves nanorods, which are expected to interact with larger portions of endothelial cell (EC) membranes, due to surface area of the nanorod long axis. Conventional nanorod diameters are orders of magnitude larger than the GCX pore size, so we adapted conventional synthesis methods to fabricate ultrasmall gold nanorods …},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baldwin2019nanoformulation,

title = {Nanoformulation of talazoparib delays tumor progression and ascites formation in a late stage cancer model},

author = {Paige Baldwin and Anders W Ohman and Jamie Edward Medina and Eric Timothy McCarthy and Daniela M Dinulescu and Srinivas Sridhar},

year  = {2019},

date = {2019-01-01},

journal = {Frontiers in oncology},

volume = {9},

pages = {353},

publisher = {Frontiers},

abstract = {Talazoparib, a potent PARP inhibitor, induces synthetic lethality in BRCA-deficient cancers making it an attractive candidate for ovarian cancer treatment. However, its potency lends itself to side effects associated more closely with traditional chemotherapeutics than other clinically approved PARP inhbitors. We sought to formulate Talazoparib in a nanoparticle delivery system, which allows the drug to be administered intraperitoneally. This was done to specifically target peritoneal dissemination of late stage metastatic ovarian cancer and increase talazoparib’s therapeutic efficacy while minimizing toxic side effects. NanoTalazoparib was developed and characterized with regard to its size, loading, and surface charge. Talazoparib and NanoTalazoparib were tested on a panel of murine and human BRCA cell lines and the dose response was compared to Olaparib’s, the currently used PARP inhibitor. Therapeutic efficacy was tested in vivo in a Brca peritoneal cancer model that mimics late stage disseminated disease. NanoTalazoparib has a diameter of about 70 nm with a neutral surface charge and ~75% encapsulation efficiency, which slowly releases the drug over several hours. Dose response analysis indicated that the murine cell lines with conditional BRCA1/2, PTEN, and TP53 deletions had the lowest IC50s. NanoTalazoparib administered on a schedule of three doses weekly slowed disease progression and resulted in significantly less mice with ascites at the end point compared to controls. These results indicate that the slow release nanoformulation, NanoTalazoparib, effectively delivers PARP inhibitor therapy to the peritoneal cavity for …},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{versek2019portable,

title = {Portable system for neuro-optical diagnostics using virtual reality display},

author = {Craig Versek and Armen Rissmiller and Anthony Tran and Munish Taya and Kaushik Chowdhury and Peter Bex and Srinivas Sridhar},

year  = {2019},

date = {2019-01-01},

journal = {Military medicine},

volume = {184},

number = {Supplement_1},

pages = {584--592},

publisher = {Oxford University Press},

abstract = {A new product prototype system for diagnosing vision and neurological disorders, called NeuroDotVR, is described herein: this system utilizes a novel wireless NeuroDot brain sensor [Versek C et al. J Neural Eng. 2018 Aug; 15(4):046027] that quantitatively measures visual evoked potentials and fields resulting from custom visual stimuli displayed on a smartphone housed in a virtual reality headset. The NeuroDot brain sensor is unique in that it can be operated both in regular electroencephalography mode, as well as a new electric field encephalography mode, which yields improvements in signal sensitivity and provides new diagnostic information. Steady state and transient visual evoked potentials and fields using reversing checkerboard stimuli are presented with case studies in amblyopia, glaucoma, and dark adaptation. These preliminary data sets highlight potential clinical applications that may be …},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{di2019nano,

title = {A nano-liposome formulation of the PARP inhibitor Talazoparib enhances treatment efficacy and modulates immune cell populations in mammary tumors of BRCA-deficient mice},

author = {Paige Baldwin Di Zhang and Ana S Leal and Sarah Carapellucci and Srinivas Sridhar and Karen T Liby},

year  = {2019},

date = {2019-01-01},

journal = {Theranostics},

volume = {9},

number = {21},

pages = {6224},

publisher = {Ivyspring International Publisher},

abstract = {Two recently approved PARP inhibitors provide an important new therapeutic option for patients with BRCA-mutated metastatic breast cancer. PARP inhibitors significantly prolong progression-free survival in patients, but conventional oral delivery of PARP inhibitors is hindered by limited bioavailability and off-target toxicities, thus compromising the therapeutic benefits and quality of life for patients. Here, we developed a new delivery system, in which the PARP inhibitor Talazoparib is encapsulated in the bilayer of a nano-liposome, to overcome these limitations.



Methods: Nano-Talazoparib (NanoTLZ) was characterized both in vitro and in vivo. The therapeutic efficacy and toxicity of Nano-Talazoparib (NanoTLZ) were evaluated in BRCA-deficient mice. The regulation of NanoTLZ on gene transcription and immunomodulation were further investigated in spontaneous BRCA-deficient tumors.



Results: NanoTLZ significantly (p<0.05) prolonged the overall survival of BRCA-deficient mice compared to all of the other experimental groups, including saline control, empty nanoparticles, and free Talazoparib groups (oral and i.v.). Moreover, NanoTLZ was better tolerated than treatment with free Talazoparib, with no significant weight lost or alopecia as was observed with the free drug. After 5 doses, NanoTLZ altered the expression of over 140 genes and induced DNA damage, cell cycle arrest and inhibition of cell proliferation in the tumor. In addition, NanoTLZ favorably modulated immune cell populations in vivo and significantly (p<0.05) decreased the percentage of myeloid derived suppressor cells in both the tumor and spleen compared to control groups.



Conclusions: Our results demonstrate that delivering nanoformulated Talazoparib not only enhances treatment efficacy but also reduces off-target toxicities in BRCA-deficient mice; the same potential is predicted for patients with BRCA-deficient breast cancer.



Keywords: PARP inhibitor, Talazoparib, Nanoparticle, BRCA-deficient breast cancer, immunomodulation},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kunjachan2019selective,

title = {Selective priming of tumor Blood Vessels by Radiation therapy enhances nanodrug Delivery},

author = {Sijumon Kunjachan and Shady Kotb and Robert Pola and Michal Pechar and Rajiv Kumar and Bijay Singh and Felix Gremse and Reza Taleeli and Florian Trichard and Vincent Motto-Ros and others},

year  = {2019},

date = {2019-01-01},

journal = {Scientific reports},

volume = {9},

number = {1},

pages = {1--14},

publisher = {Nature Publishing Group},

abstract = {Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baldwin2019nanoformulationb,

title = {Nanoformulation of talazoparib increases maximum tolerated doses in combination with temozolomide for treatment of Ewing sarcoma},

author = {Paige Baldwin and Rostislav Likhotvorik and Nabeela Baig and Jodie Cropper and Ruth Carlson and Raushan Kurmasheva and Srinivas Sridhar},

year  = {2019},

date = {2019-01-01},

journal = {Frontiers in Oncology},

volume = {9},

pages = {1416},

publisher = {Frontiers},

abstract = {The Pediatric Preclinical Testing Program previously identified the PARP inhibitor talazoparib (TLZ) as a means to potentiate temozolomide (TMZ) activity for the treatment of Ewing sarcoma. However, the combination of TLZ and TMZ has been toxic in both preclinical and clinical testing, necessitating TMZ dose reduction to ~15% of the single agent maximum tolerated dose. We have synthesized a nanoparticle formulation of talazoparib (NanoTLZ) to be administered intravenously in an effort to modulate the toxicity profile of this combination treatment. Results in Ewing sarcoma xenograft models are presented to demonstrate the utility of this delivery method both alone and in combination with TMZ. NanoTLZ reduced gross toxicity and had a higher maximum tolerated dose than oral TLZ. The dose of TMZ did not have to be reduced when combined with NanoTLZ as was required when combined with oral TLZ. This indicated the NanoTLZ delivery system may be advantageous in decreasing the systemic toxicity associated with the combination of oral TLZ and TMZ.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{cheng2018synthesis,

title = {Synthesis of functionalized 10-nm polymer-coated gold particles for endothelium targeting and drug delivery},

author = {Ming J Cheng and Priya Prabakaran and Rajiv Kumar and Srinivas Sridhar and Eno E Ebong},

year  = {2018},

date = {2018-01-01},

journal = {JoVE (Journal of Visualized Experiments)},

number = {131},

pages = {e56760},

abstract = {Gold nanoparticles (AuNPs) have been used extensively in medical research due to their size, biocompatibility, and modifiable surface. Specific targeting and drug delivery are some of the applications of these AuNPs, but endothelial extracellular matrices' defensive properties hamper particle uptake. To address this issue, we describe a synthesis method for ultrasmall gold nanoparticles to improve vascular delivery, with customizable functional groups and polymer lengths for further adjustments. The protocol yields 2.5 nm AuNPs that are capped with tetrakis(hydroxymethyl)phosphonium chloride (THPC). The replacement of THPC with hetero-functional polyethylene glycol (PEG) on the surface of the AuNP increases the hydrodynamic radius to 10.5 nm while providing various functional groups on the surface. The last part of the protocol includes an optional addition of a fluorophore to allow the AuNPs to be visualized under fluorescence to track nanoparticle uptake. Dialysis and lyophilization were used to purify and isolate the AuNPs. These fluorescent nanoparticles can be visualized in both in vitro and in vivo experiments due to the biocompatible PEG coating and fluorescent probes. Additionally, the size range of these nanoparticles render them an ideal candidate for probing the glycocalyx without disrupting normal vasculature function, which may lead to improved delivery and therapeutics.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{gharagouzloo2018dataset,

title = {Dataset on a 173 region awake resting state quantitative cerebral blood volume rat brain atlas and regional changes to cerebral blood volume under isoflurane anesthetization and CO2 challenge},

author = {Codi A Gharagouzloo and Liam Timms and Ju Qiao and Zihang Fang and Joseph Nneji and Aniket Pandya and Praveen Kulkarni and Anne L van de Ven and Craig Ferris and Srinivas Sridhar},

year  = {2018},

date = {2018-01-01},

journal = {Data in brief},

volume = {17},

pages = {393--396},

publisher = {Elsevier},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{kunjachan2018targeted,

title = {Targeted Drug Delivery by Radiation-Induced Tumor Vascular Modulation},

author = {Sijumon Kunjachan and Shady Kotb and Rajiv Kumar and Robert Pola and Michal Pechar and Felix Gremse and Reza Taleeli and Florian Trichard and Vincent Motto-Ros and Lucie Sancey and others},

year  = {2018},

date = {2018-01-01},

journal = {bioRxiv},

pages = {268714},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Effective drug delivery is severely restricted by the presence of complex pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, mature and hypopermeable tumor blood vessels limit the permeation and penetration of chemo or nanotherapeutics to cancer cells and substantially reduce the treatment efficacy. New, clinically-viable strategies are therefore sought to breach the neoplastic barriers that prevent optimal tumor-specific drug delivery. Here, we present an original idea to boost targeted drug delivery by selectively knocking down the tumor vascular barrier in a poorly permeable human pancreatic cancer model. For the first time, we demonstrate that clinical irradiation (10 Gy, 6 MV) can induce tumor vascular modulation when combined with tumor endothelial-targeting gold nanoparticles. Active disruption of tumor blood vessels by nanoparticle-combined radiotherapy led to increased vessel permeability and improved tumor uptake of two prototypical model nanodrugs: i) a short-circulating nanocarrier with MR-sensitive gadolinium (Gad-NC; 8 kDa; t1/2=1.5 h) and ii) a long-circulating nanocarrier with fluorescence-sensitive NIR dye (FL-NC; 30 kDa; t1/2=25 h). Functional changes in the altered tumor vessel dynamics, measured by relative changes in permeability (Ktrans), flux rate (Kep) and extracellular interstitial volume (Ve) were consistent with the concomitant increase in nanodrug delivery. This combination of radiation-induced antivascular and nanodrug-mediated anti-tumor treatment offers high therapeutic benefit for tumors with pathophysiology that restricts efficient drug delivery},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{gupta2018synthesis,

title = {Synthesis and in vitro studies of PLGA-DTX nanoconjugate as potential drug delivery vehicle for oral cancer},

author = {Parul Gupta and Manjri Singh and Rajiv Kumar and Jodi Belz and Rishi Shanker and Premendra D Dwivedi and Srinivas Sridhar and Surinder P Singh},

year  = {2018},

date = {2018-01-01},

journal = {International journal of nanomedicine},

volume = {13},

number = {T-NANO 2014 Abstracts},

pages = {67},

publisher = {Dove Press},

abstract = {Advances in nanotechnology have led to the design of multifunctional nanoparticles capable of cellular imaging, targeted drug delivery, and diagnostics for early cancer detection. We synthesized poly(lactic-co-glycolic acid) nanoparticles encapsulating a model radiosensitizing drug docetaxel accomplishing localized in situ delivery of the sensitizer to the tumor site. The synthesized nanoparticles have been characterized for their physicochemical properties. The in vitro cytotoxicity of drug-loaded nanoparticles has been studied on human tongue carcinoma cell line SCC-9 (ATCC-CRL-1629).},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baronia2018synthesis,

title = {Synthesis and characterization of multifunctional gold nanoclusters for application in radiation therapy},

author = {Richa Baronia and Manjri Singh and Rajat B Gupta and Stalin Karuppiah and Rajiv Kumar and Jodi Belz and Rishi Shanker and Srinivas Sridhar and Surinder P Singh},

year  = {2018},

date = {2018-01-01},

journal = {International journal of nanomedicine},

volume = {13},

number = {T-NANO 2014 Abstracts},

pages = {113},

publisher = {Dove Press},

abstract = {Gold nanoparticles, because of their high radiation absorption coefficient and efficient generation of secondary photoelectrons, have been predicted to enhance therapeutic efficacy in radiation therapy. However, high dose for effective treatment limits their use. We have synthesized multifunctional gold nanoclusters (GNCs) that can be used for imaging and radiation therapy. The designed GNCs have been characterized for their physicochemical properties, biocompatibility, and their radiation dose enhancement potential on PC3 cell lines.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baldwin2018vitro,

title = {In vitro analysis of pArp inhibitor nanoformulations},

author = {Paige Baldwin and Shifalika Tangutoori and Srinivas Sridhar},

year  = {2018},

date = {2018-01-01},

journal = {International journal of nanomedicine},

volume = {13},

number = {T-NANO 2014 Abstracts},

pages = {59},

publisher = {Dove Press},

abstract = {PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecular inhibitors as a monotherapy in inhibiting colony formation suggests enhanced efficacy of these treatments in combination with other therapies, even in tumors which have developed resistance.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{upponi2018polymeric,

title = {Polymeric micelles: Theranostic co-delivery system for poorly water-soluble drugs and contrast agents},

author = {Jaydev R Upponi and Kaushal Jerajani and Dattatri K Nagesha and Praveen Kulkarni and Srinivas Sridhar and Craig Ferris and Vladimir P Torchilin},

year  = {2018},

date = {2018-01-01},

journal = {Biomaterials},

volume = {170},

pages = {26--36},

publisher = {Elsevier},

abstract = {Interest in theranostic agents has continued to grow because of their promise for simultaneous cancer detection and therapy. A platform-based nanosized combination agent suitable for the enhanced diagnosis and treatment of cancer was prepared using polymeric polyethylene glycol-phosphatidylethanolamine-based micelles loaded with both, poorly soluble chemotherapeutic agent paclitaxel and hydrophobic superparamagnetic iron oxide nanoparticles (SPION), a Magnetic Resonance Imaging contrast agent. The co-loaded paclitaxel and SPION did not affect each other's functional properties in vitro. In vivo, the resulting paclitaxel-SPION-co-loaded PEG-PE micelles retained their Magnetic Resonance contrast properties and apoptotic activity in breast and melanoma tumor mouse models. Such theranostic systems are likely to play a significant role in the combined diagnosis and therapy that leads to a more personalized and effective form of treatment.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{versek2018electric,

title = {Electric field encephalography for brain activity monitoring},

author = {C Versek and T Frasca and J Zhou and K Chowdhury and S Sridhar},

year  = {2018},

date = {2018-01-01},

journal = {Journal of neural engineering},

volume = {15},

number = {4},

pages = {046027},

publisher = {IOP Publishing},

abstract = {Objective. We describe an early-stage prototype of a new wireless electrophysiological sensor system, called NeuroDot, which can measure neuroelectric potentials and fields at the scalp in a new modality called Electric Field Encephalography (EFEG). We aim to establish the physical validity of the EFEG modality, and examine some of its properties and relative merits compared to EEG. Approach. We designed a wireless neuroelectric measurement device based on the Texas Instrument ADS1299 Analog Front End platform and a sensor montage, using custom electrodes, to simultaneously measure EFEG and spatially averaged EEG over a localized patch of the scalp (2 cm  ×  2 cm). The signal properties of each modality were compared across tests of noise floor, Berger effect, steady-state visually evoked potential (ssVEP), signal-to-noise ratio (SNR), and others. In order to compare EFEG to EEG modalities in the frequency domain, we use a novel technique to compute spectral power densities and derive narrow-band SNR estimates for ssVEP signals. A simple binary choice brain–computer-interface (BCI) concept based on ssVEP is evaluated. Also, we present examples of high quality recording of transient Visually Evoked Potentials and Fields (tVEPF) that could be used for neurological studies. Main results. We demonstrate the capability of the NeuroDot system to record high quality EEG signals comparable to some recent clinical and research grade systems on the market. We show that the locally-referenced EFEG metric is resistant to certain types of movement artifacts. In some ssVEP based measurements, the EFEG modality shows promising results, demonstrating superior signal to noise ratios than the same recording processed as an analogous EEG signal. We show that by using EFEG based ssVEP SNR estimates to perform a binary classification in a model BCI, the optimal information transfer rate (ITR) can be raised from 15 to 30 bits per minute—though these preliminary results are likely sensitive to inter-subject variations and choice of scalp locations, so require further investigation. Significance. Enhancement of ssVEP SNR using EFEG has the potential to improve visually based BCIs and diagnostic paradigms. The time domain analysis of tVEPF signals shows robust features in the electric field components that might have clinical relevance beyond classical VEP approaches.},

keywords = {Nanomedicine, Opthalmology},

pubstate = {published},

tppubtype = {article}

}

@article{guthier2018determining,

title = {Determining optimal eluter design by modeling physical dose enhancement in brachytherapy},

author = {CV Guthier and AV D'Amico and MT King and PL Nguyen and PF Orio and S Sridhar and GM Makrigiorgos and RA Cormack},

year  = {2018},

date = {2018-01-01},

journal = {Medical physics},

volume = {45},

number = {8},

pages = {3916--3925},

abstract = {Purpose

In situ drug release concurrent with radiation therapy has been proposed to enhance the therapeutic ratio of permanent prostate brachytherapy. Both brachytherapy sources and brachytherapy spacers have been proposed as potential eluters to release compounds, such as nanoparticles or chemotherapeutic agents. The relative effectiveness of the approaches has not been compared yet. This work models the physical dose enhancement of implantable eluters in conjunction with brachytherapy to determine which delivery mechanism provides greatest opportunity to enhance the therapeutic ratio.



Materials and methods

The combined effect of implanted eluters and radioactive sources were modeled in a manner that allowed the comparison of the relative effectiveness of different types of implantable eluters over a range of parameters. Prostate geometry, source, and spacer positions were extracted from treatment plans used for 125I permanent prostate implants. Compound concentrations were calculated using steady‐state solution to the diffusion equation including an elimination term characterized by the diffusion‐elimination modulus (ϕb). Does enhancement was assumed to be dependent on compound concentration up to a saturation concentration (csat). Equivalent uniform dose (EUD) was used as an objective to determine the optimal configuration of eluters for a range of diffusion‐elimination moduli, concentrations, and number of eluters. The compound delivery vehicle that produced the greatest enhanced dose was tallied for points in parameter space mentioned to determine the conditions under whether there are situations where one approach is preferable to the other.



Results

The enhanced effect of implanted eluters was calculated for prostate volumes from 14 to 45 cm3, ϕb from 0.01 to 4 mm−1, csat from 0.05 to 7.5 times the steady‐state compound concentration released from the surface of the eluter. The number of used eluters (ne) was simulated from 10 to 60 eluters. For the region of (c sat , Φ)‐space that results in a large fraction of the gland being maximally sensitized, compound eluting spacers or sources produce equal increase in EUD. In the majority of the remaining (c sat , Φ)‐space, eluting spacers result in a greater EUD than sources even where sources often produce greater maximal physical dose enhancement. Placing eluting implants in planned locations throughout the prostate results in even greater enhancement than using only source or spacer locations.



Conclusions

Eluting brachytherapy spacers offer an opportunity to increase EUD during the routine brachytherapy process. Incorporating additional needle placements permits compound eluting spacer placement independent of source placement and thereby allowing a further increase in the therapeutic ratio. Additional work is needed to understand the in vivo spatial distribution of compound around eluters, and to incorporate time dependence of both compound release and radiation dose.



},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{zhang2018nanoformulated,

title = {Nanoformulated Talazoparib enhances the efficacy and reduces the toxicity of this PARP inhibitor in a preclinical model of BRCA-deficient breast cancer},

author = {Di Zhang and Paige Baldwin and Srinivas Sridhar and Karen Liby},

year  = {2018},

date = {2018-01-01},

journal = {The FASEB Journal},

volume = {32},

number = {1_supplement},

pages = {565--10},

publisher = {The Federation of American Societies for Experimental Biology},

abstract = {BRCA mutations are the leading cause of hereditary breast cancer. PARP inhibitors have shown promising activities in clinical trials for breast cancer by inducing synthetic lethality, particularly in patients with BRCA deficiency. Moreover, the utility of PARP inhibitors could potentially extend beyond BRCA mutations by targeting defects in homologous recombination, and thus impact up to 75% of triple negative breast cancer patients and 33% of breast cancer patients overall. However, conventional oral delivery of PARP inhibitors is hindered by limited bioavailability and significant off-target toxicities, thus compromising the therapeutic benefits and quality of life in patients. Therefore, we developed a new nanoparticle delivery system for PARP inhibitors and hypothesize that nanoformulated Talazoparib can enhance efficacy by increasing drug concentrations in the tumor and reduce off-target toxicities. The nanoparticle formulation includes polymer brushes to prolong the circulation time, enabling tumor accumulation through the enhanced permeability and retention effect. The therapeutic efficacy of Nano-Talazoparib (Nano-TLZ) was assessed after i.v. injection in Brca1Co/Co;MMTV-Cre; p53+/− mice with established tumors and compared to vehicle control (saline, i.v.), empty nanoparticles (i.v.), free Talazoparib (i.v.), and free Talazoparib (gavage). Treatment was started when the tumor was 4 mm in diameter and ended when the tumor size reached defined IACUC endpoints. Nano-TLZ significantly (p<0.05) prolonged the life span of BRCA deficient mice from 11.6±2.6 days with saline injection and 18.3±3.6 days with empty nanoparticles injection to 82.2±10.5 days with i.v. Nano-TLZ. Nano-TLZ induced growth arrest in 100% of the tumors and regression (> 50% reduction in tumor volume) in 80% of the tumors. Established tumors regressed more rapidly, and therefore progression free survival significantly improved in the nanoformulated Talazoparib group (p<0.05). Moreover, Nano-TLZ is better tolerated than free Talazoparib with no significant weight lost or alopecia. In a biomarker study following 10 days of treatment, Nano-TLZ increased double strand DNA breaks (γ-H2AX) and decreased proliferation (PCNA) compared to the saline controls. Interestingly, Nano-TLZ significantly (p<0.05) decreased myeloid derived suppressor cells in both the tumor (41.6±4.7% to 11.2±2.9%) and spleen (10.0±3.2% to 3.7±0.6%) compared to the saline control. Nano-TLZ also significantly (p<0.05) decreased the percentage of tumor-associated macrophages in the mammary gland from 7.4±2.0% in the saline control group to 2.5±0.2% in the Nano-TLZ group. The changes in immune populations suggest potential immunomodulatory effects of Talazoparib. These results demonstrate that the delivery of Talazoparib as a nanoformulation induces superior treatment outcomes with reduced off-target toxicity in BRCA deficient mice, and provides a novel delivery strategy for PARP inhibitors in patients.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{mitra2018comparative,

title = {The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation},

author = {Ronodeep Mitra and Ju Qiao and Sudharsan Madhavan and Gerard L O’Neil and Bailey Ritchie and Praveen Kulkarni and Srinivas Sridhar and Anne L van de Ven and Erica Cherry M Kemmerling and Craig Ferris and others},

year  = {2018},

date = {2018-01-01},

journal = {Translational medicine communications},

volume = {3},

number = {1},

pages = {1--15},

publisher = {BioMed Central},

abstract = {Background and aims

Endothelial surface glycocalyx shedding plays a role in endothelial dysfunction and increases vessel wall permeability, which can lead to inflammation and atherogenesis. We sought to elucidate whether a high fat diet (HFD) or disturbed blood flow conditions, both of which are atherogenic risk factors, would contribute more detrimentally to pre-atherosclerotic loss of endothelial glycocalyx integrity and vascular inflammation.



Methods

Six to seven week-old C57BL/6-background apolipoprotein-E-knockout (ApoE-KO) male mice were either fed a chow diet, fed a modified Western HFD, and/or subjected to a partial left carotid artery (LCA) ligation procedure to induce disturbed blood flow patterns in the LCA. Mice were sacrificed after 1 week of experimental conditions. Both LCA and right carotid artery (RCA) vessels were dissected and preserved to compare glycocalyx coverage and thickness as well as macrophage accumulation in carotid arterial walls amongst and between cohorts.



Results

Glycocalyx coverage of the endothelium was significantly reduced in the LCAs of HFD fed mice when compared to the control. More significant reduction in glycocalyx coverage occurred in the LCAs of mice exposed to disturbed flow by partial LCA ligation when compared to the control. No differences were found in glycocalyx coverage of RCAs from all cohorts. Regarding inflammation, no difference in macrophage accumulation in carotid arterial walls was observed when comparing the LCAs and RCAs of control and HFD fed mice. However, macrophage infiltration in vessel walls showed a 20-fold increase in the LCAs exposed to disturbed flow following ligation, when compared to control LCAs, while no such statistical difference was observed between the RCAs of the group.



Conclusions

In our mouse model, endothelial glycocalyx integrity was compromised more by disturbed blood flow patterns than by exposure of the carotid vessel to HFD conditions. The pathophysiological implications include endothelial dysfunction, which correlates to macrophage infiltration in vessel walls and promotes atherogenesis.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}

@article{baldwin2018intraperitoneal,

title = {Intraperitoneal delivery of NanoOlaparib for disseminated late-stage cancer treatment},

author = {Paige Baldwin and Anders W Ohman and Shifalika Tangutoori and Daniela M Dinulescu and Srinivas Sridhar},

year  = {2018},

date = {2018-01-01},

journal = {International journal of nanomedicine},

volume = {13},

pages = {8063},

publisher = {Dove Press},

abstract = {Background

PARP inhibitors, such as Olaparib, have advanced the treatment of ovarian cancer by providing patients with an effective and molecularly-targeted maintenance therapy. However, all orally-administered drugs, including Olaparib, must undergo first-pass metabolism. In contrast, a nanoparticle delivery system has the advantage of administering Olaparib directly into the peritoneal cavity for local treatment. Consequently, we sought to optimize the sustained-release formulation NanoOlaparib, previously deemed effective as an intravenous solid tumor treatment, for the local treatment of disseminated disease via intraperitoneal (i.p.) therapy.



Methods

The tumor cell line 404, which was derived from a Brca2−/−, Tp53−/−, Pten−/− genetically engineered mouse model, exhibited high sensitivity to Olaparib in vitro. It was chosen for use in developing an i.p. spread xenograft for testing nanotherapy efficacy in vivo. NanoOlaparib as a monotherapy or in combination with cisplatin was compared to oral Olaparib alone or in combination using two different dose schedules. A pilot biodistribution study was performed to determine drug accumulation in various organs following i.p. administration.



Results

Daily administration of NanoOlaparib reduced tumor growth and decreased the variability of the treatment response observed with daily oral Olaparib administration. However, systemic toxicity was observed in both the NanoOlaparib and vehicle (empty nanoparticle) treated groups. Scaling back the administration to twice weekly was well tolerated up to 100 mg/kg but reduced the effect on tumor growth. Biodistribution profiles indicated that NanoOlaparib began accumulating in tissues within an hour of administration and persisted for at least 72 hours after a single dose, exiting the peritoneal cavity faster than expected.



Conclusion

NanoOlaparib must be modified for use against disseminated disease. Future avenues to develop NanoOlaparib as an i.p. therapy include a modified surface-coating to retain it in the peritoneal cavity and prevent entry into systemic circulation, in addition to targeting moieties for localization in tumor cells.},

keywords = {Nanomedicine},

pubstate = {published},

tppubtype = {article}

}