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miR-205 Nanoparticle system circumvents docetaxel resistance in prostate cancer

Award Number: SC1GM139727
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/18/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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miR-205 Nanoparticle system circumvents docetaxel resistance in prostate cancer - Modified Project Summary/Abstract Section The current SC01 application aims to develop a program that increases the research competitiveness of Dr. Yallapu at the University of Texas Rio Grande Valley (UTRGV). The UTRGV has historical mission and track record of training and graduating students in basic science and biomedical research. In this application, Dr. Yallapu proposed to achieve a microRNA Nanoparticle formulation which can circumvent docetaxel resistance in prostate cancer. Loss of tumor suppressor miRNAs in cancer cells promotes cancer tumorigenesis and progression. However, the efficient delivery of miRNAs to target tumor tissues is a major challenge in the transition of miRNA therapy to the clinic. The current approaches to deliver miRNAs not only introduce the risk, associated with virus-based carriers but also systemic toxicity and low therapeutic outcome. To address these challenges and barriers use of nanoparticle mediated delivery is implemented which can offer protection to miRNA in the blood stream and accumulation at the tumor site which can enhance efficiency of therapy. Thus, the objective of this study is to employ dual layer magnetic nanoparticle systems that are constructed to release miRNA at tumor sites. This nanoparticle formulation can be applied for improved systemic bioavailability, low toxicity, and tumor targeting of therapeutics. The nanoparticle therapies are highly suitable to target and treat resistant tumors (castration resistant prostate cancer, CRPC) that affects thousands of men each year. Recent studies demonstrate miR-205 loss is correlated with prostate cancer (PrCa) progression, metastasis, and drug resistance. Restoration of miR-205 induces pro-apoptotic, anti-proliferative, and epigenetic modulator roles. Literature and our preliminary data suggest re-expression of miR-205 in PrCa cells/tumors result in sensitizing cells to chemotherapy, reverses drug resistance, EMT regulation, and suppression of PrCa growth. Therefore, the central hypothesis of this proposal is that dual layered magnetic nanoparticles can enhance the loading capacity of miRNA per particle and delivery to PrCa cells. This study aims to 1) delineate development of miR-205 nanoparticle formulation, performing its physico-chemical and biological fate, mechanistic investigations of in vitro uptake, intercellular accumulation of the miRNA, and 2) study in vivo tracking and biodistribution miR-205 in nanoparticles, and 3) examination target gene modulation, and 4) determine improved chemosensitization potential for docetaxel in drug resistant PrCa cells and relevant orthotopic mouse models. The clinical outcome led us to develop a unique microRNA nanoplatform, which can be efficient in inhibiting oncogenic pathways that are linked to drug resistance. Additionally, this award enables Dr. Yallapu to improve and obtain high quality/quantity of preliminary data and publications to be able to succeed in acquiring non-SCORE research support.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	5/14/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $363,250 )
2024	2024	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	4	3/25/2024	NON-COMPETING CONTINUATION	$326,925
2024	2024	THE UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	001	4	6/18/2024	NON-COMPETING CONTINUATION	$36,325
														Subtotal = $363,250

Issue Date FY: 2023 ( Subtotal = $363,250 )
2023	2023	UNIVERSITY OF TEXAS RIO GRANDE VALLEY	1201 W UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	3	3/16/2023	NON-COMPETING CONTINUATION	$363,250
														Subtotal = $363,250

Issue Date FY: 2022 ( Subtotal = $363,250 )
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	2	3/31/2022	NON-COMPETING CONTINUATION	$326,925
2022	2022	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	001	2	6/14/2022	NON-COMPETING CONTINUATION	$36,325
														Subtotal = $363,250

Issue Date FY: 2021 ( Subtotal = $363,250 )
2021	2021	UNIVERSITY OF TEXAS RIO GRANDE VALLEY, THE	1201 WEST UNIVERSITY DR	EDINBURG	TX	78539	HIDALGO	USA	Biomedical Research and Research Training	000	1	5/18/2021	NEW	$363,250
														Subtotal = $363,250

Grand Total All Awards = $1,453,000

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miR-205 Nanoparticle system circumvents docetaxel resistance in prostate cancer

Award Number: SC1GM139727

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/18/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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