Publications

@article{sridhar2023trueb,

title = {True superconductivity at near ambient temperature has not been confirmed by Dasenbrock-Gammon et al. Nature, volume 615, pages 244–250 (2023)},

author = {Srinivas Sridhar},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Journal of Physics and Chemistry of Solids},

pages = {111381},

publisher = {Pergamon},

keywords = {Superconductivity},

pubstate = {published},

tppubtype = {article}

}

@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{sridhar2023true,

title = {True superconductivity at near ambient temperature has not been confirmed by Dasenbrock-Gammon, et. al. Nature (2023)},

author = {Srinivas Sridhar},

year  = {2023},

date = {2023-01-01},

journal = {arXiv preprint arXiv:2303.05987},

keywords = {},

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{cohen2021adapting,

title = {Adapting undergraduate research to remote work to increase engagement},

author = {Susan E Cohen and Sara M Hashmi and A-Andrew D Jones III and Vasiliki Lykourinou and Mary Jo Ondrechen and Srinivas Sridhar and Anne L Ven and Lauren S Waters and Penny J Beuning},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {The Biophysicist},

volume = {2},

number = {2},

pages = {28–32},

publisher = {Biophysical Society},

keywords = {Education},

pubstate = {published},

tppubtype = {article}

}

@article{versek2021portable,

title = {Portable diagnostic system for age-related macular degeneration screening using visual evoked potentials},

author = {Craig Versek and S Mohammad Ali Banijamali and Peter Bex and Kameran Lashkari and Sagar Kamarthi and Srinivas Sridhar},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Eye and brain},

pages = {111–127},

publisher = {Taylor & Francis},

keywords = {Neurotechnology},

pubstate = {published},

tppubtype = {article}

}

@article{timms2021ferumoxytol,

title = {Ferumoxytol-enhanced ultrashort TE MRA and quantitative morphometry of the human kidney vasculature},

author = {Liam Timms and Tianyi Zhou and Yue Lyu and Ju Qiao and Vishala Mishra and Rita Maria Lahoud and Gayatri Veeramani Jayaraman and Andrew S Allegretti and David Drew and Ravi T Seethamraju and others},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Abdominal Radiology},

volume = {46},

pages = {3288–3300},

publisher = {Springer US},

keywords = {MRI},

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{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{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{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{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{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{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{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{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{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{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{versek2020portableb,

title = {Portable Objective Diagnostics using Visual Evoked Potentials for Age-related Macular Degeneration},

author = {Craig Versek and S Mohammad Ali Banijamali and Peter J Bex and Kameran Lashkari and Sagar V Kamarthi and Srinivas Sridhar},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {medRxiv},

pages = {2020–01},

publisher = {Cold Spring Harbor Laboratory Press},

keywords = {Neurotechnology},

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{versek2020portable,

title = {Portable Objective Diagnostics using Visual Evoked Potentials for Age-related Macular Degeneration},

author = {Craig William Versek and Mohammad Ali S Banijamali and Peter J Bex and Kameran Lashkari and Sagar V Kamarthi and Srinivas Sridhar},

year  = {2020},

date = {2020-01-01},

journal = {medRxiv},

publisher = {Cold Spring Harbor Laboratory Press},

abstract = {Delayed Dark Adapted vision Recovery (DAR) is a biomarker for Age-related Macular Degeneration (AMD); however, its measurement is burdensome for patients and examiners. We developed a portable, wireless, quick-setup system that employs a headset with a smartphone to deliver and analyze controlled dichoptic photobleach and pattern reversal stimuli, and with custom electroencephalography (EEG) electrodes, to measure objective Dark Adapted Visual Evoked Potentials (DAVEP) at multiple locations of the visual field in one comfortable 20-minute session, without requiring subject reporting. DAVEP responses post photobleach (up to 15 minutes), were measured concurrently in both eyes of 13 patients with AMD and 8 others not diagnosed with AMD. New unexpected features were observed in the DAVEP responses at high latencies to scotopic stimulus intensities. The amplitude recovery of the DAVEP response was significantly delayed in AMD patients compared with controls. We developed DAVEP1 scores, a simple metric for DAR, using it to successfully identify all 100% of AMD subjects and correctly classify 90% of subject eyes. Deficits in DAR in patients with AMD can be identified with this objective VEP based system using the DAVEP1 metric, a promising new objective biomarker for this disease that can be easily tested in a clinic.},

keywords = {Neurotechnology, Opthalmology},

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{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{qiao2019data,

title = {Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization},

author = {Ju Qiao and Xuezhu Cai and Qian Xiao and Zhengxi Chen and Praveen Kulkarni and Craig Ferris and Sagar Kamarthi and Srinivas Sridhar},

year  = {2019},

date = {2019-01-01},

journal = {Data in brief},

volume = {27},

pages = {104628},

publisher = {Elsevier},

abstract = {The data in this article provide details about MRI lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization (GMM-EM) algorithms. Both K-means and GMM-EM algorithms can segment lesion area from the rest of brain MRI automatically. The performance metrics (accuracy, sensitivity, specificity, false positive rate, misclassification rate) were estimated for the algorithms and there was no significant difference between K-means and GMM-EM. In addition, lesion size does not affect the accuracy and sensitivity for either method.},

keywords = {MRI},

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{sridhar2019portable,

title = {Portable VEP Diagnostics for NeuroVisual Disorders},

author = {Srinivas Sridhar and Craig Versek and Ali Banijamali and Anthony Tran and Armando Cardozo and Kameran Lashkari and Peter Bex},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Investigative Ophthalmology & Visual Science},

volume = {60},

number = {9},

pages = {3591--3591},

publisher = {The Association for Research in Vision and Ophthalmology},

abstract = {Purpose: Visual Evoked Potentials (VEPs) provide objective neuro-opthalmologic assessments that avoid patient task performance but utilizes invasive and cumbersome apparatus. We have developed a system that combines a scalp neuroelectric potential and field sensor with a smartphone in a portable wireless display headset called the NeuroDotVR (Figure 1). The system records VEPs and Fields (VEPF) in response to dichoptic stimuli presented on the smartphone display for a range of neuro-oplthalmologic disorders. We evaluate the NeuroDotVR for Dark Adaptation Recovers (DAR), a key biomarker for age-related macular degeneration (AMD).

Methods: DAR was measured simultaneously in both eyes of# patients with AMD and# age-matched controls. Following a 60s photobleach (400 cd/m 2 white cellphone screen), recovery of visual sensitivity was recorded with VEPFs to pattern reversal checkerboard …},

keywords = {Neurotechnology},

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{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{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{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}

}

@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{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{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}

}