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Ultrasound-based diagnostic and monitoring of bladder cancer treatment with drug released from nanoparticles

Funder: National Cancer Institute

Funding period
USD 350 K
Funding amount
Abstract
Project Summary/Abstract Transitional cell carcinoma (TCC) of the bladder is the fifth most common form of cancer in the United States, with over 79,000 new cases expected for 2017. For early stage carcinomas, the most common treatment regimen is to initially perform transurethral resection of bladder tumor (TURBT) using an invasive cystoscopic approach with non-specific fluorescent dyes to highlight the lesions. Even then, small lesions are often missed leading to the cancer recurring in up to 70% of patients and further progresses to advanced cancer in up to 20% of patients following TURBT. Compared to cystoscopy, high resolution ultrasound (HRUS) is low-cost, minimally invasive, and provides an in-depth view of the smooth muscle layer and surrounding tissues of the bladder with spatial resolution as low as 30 ?m. Despite advances in HRUS, current imaging systems are limited to anatomical data, as it can neither provide functional or molecular imaging data, nor facilitate any interventional approach, alone. The implementation of a targeted contrast enhancement is necessary to elevate the data acquired from even the most advanced system. Clinically approved ultrasound contrast agents operate on the principle that the speed of sound is drastically different high molecular weight gases than in soft tissue. While highly echogenic, these agents are too large and too short-lived to be useful for functional imaging. To improve upon this approach, sub-micron ultrasound agents are being used experimentally, though the resulting agents are limited and have not been applied to TCC. Clinical applications resulting from this approach will benefit by 1) improvement of current screening methods (expedited, cheaper and dynamic), and 2) facilitation of specific delivery of intravesical treatment, specifically with non-invasive monitoring. We propose a material based on mesoporous silica nanoparticles (MSN), functionalized for diagnostic HRUS as well as interventional imaging following delivery of a therapeutic agent. We propose a rigorous in vitro / in vivo testing methodology to characterize the MSN and optimize its diagnostic and therapeutic capabilities. Upon completion the MSN would fulfill a desperately needed alternative to the current invasive and TCC treatment. If successful, the end product represents a highly marketable cost effective material that can be deployed clinically, ultimately improving patient outcomes. Our team of biomedical engineers, radiologists, urology researchers and clinicians are uniquely poised to carry out this research. The use of biocompatible materials and a short peptide for targeting, as opposed to many pre-clinical studies which involve monoclonal antibodies, ensures that the proposed material is of immediate clinical and commercial relevance. This proposal paves the way for SBIR Phase II studies, in which long-term survival and the scale-up of synthesis for commercial purposes will be evaluated.

 
94
Projects
USD 65.7 M
Aggregated funding amount
USD 792 K
Average funding amount
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
Modulation of regulatory T cells in the bladder tumor environment by anti-PD-L1 immunotherapy

Bladder Cancer Advocacy Network to David Yoonsuk Oh, Lawrence Fong

USD 50,000
2018 - 2019
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Novel Biomarkers for the Clinical Management of Bladder Cancer

National Cancer Institute to VINATA B LOKESHWAR

USD 466,211
2018 - 2023
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Intra-operative MRI-guided Robotic System for Photothermal Therapy of Bladder Cancer

University Grants Committee to Kwok Ka Wai, TEOH Yuen Chun Jeremy, Vardhanabhuti Varut Vince, Wong Kenneth Kin Yip

USD 80,682
2018 - 2021
Project list item
Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR study).

University Grants Committee to TEOH Yuen Chun Jeremy

USD 75,274
2018 - 2020
Project list item
Non invasive Cell Based Liquid Biopsy Platform for Bladder Cancer

European Commission

USD 4,291,985
2017 - 2020
Project list item
INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

National Cancer Institute to ROSA MARIA DIAZ, LUKKANA SUKSANPAISAN, BRADLEY C. LEIBOVICH

USD 1,081,593
2017 - 2020
Project list item
Improved detection of bladder cancer recurrence using a biophysical biomarker

National Cancer Institute to MICHAEL D HENRY

USD 299,860
2017 - 2019
Project list item
Translation of a Clinical Molecular Diagnostic Assay for Bladder Cancer

National Cancer Institute to STEVE GOODISON

USD 1,238,725
2017 - 2022
Project list item
The Role of EZH2 in Non-Muscle Invasive Bladder Cancer

United States Department of Veterans Affairs to JOSHUA JAMES MEEKS

 
2016 - 2020
Project list item
Understanding barriers to single-dose intravesical chemotherapy in non-muscle invasive bladder cancer

National Cancer Institute to KELLY CLINTON CARY

USD 433,019
2016 - 2021
Project list item
Early clinical testing of intravesical administration of the muco-adherent, docetaxel-laden polymer STK-01 in bladder cancer.

Canadian Institutes of Health Research to Alan I So, Peter Colin Black

USD 225,587
2016 - 2019
Project list item
BladderPath: Image Directed Redesign of Bladder Cancer Treatment Pathways

NIHR Evaluation Trials and Studies Coordinating Centre to Nicholas James

USD 1,974,056
2016 - 2021
Project list item
Visible Light-Controlled Combination Strategy for Treating Nonmuscle Invasive Bladder Cancers

Congressionally Directed Medical Research Programs to Youngjae You

USD 592,000
2015 - 2016
Project list item
bLadder cAncer URine cEll aNalysis

European Commission

USD 3,534,487
2015 - 2018
Project list item
UROthelial carcinoma Biomarker based diagnostic tEST

European Commission

USD 55,489
2015 - 2015
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