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Testing in-situ formed nanofibers for inhibiting metastatic osteosarcoma (mOS) in murine models

Award Number: R03CA262920
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/09/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Testing in-situ formed nanofibers for inhibiting metastatic osteosarcoma (mOS) in murine models - Abstract The treatment outcome of metastatic osteosarcoma (mOS) remains poor and has not improved for over four decades. Thus, developing novel approaches for treating mOS is urgently needed. We unexpectedly find that enzyme-instructed self-assembly (EISA) is able to form nanofibers (NFs) inside the nuclei of mOS cells and selectively killing the mOS cells in cell culture. This proposed pilot study is to test the in-situ formed NFs for inhibiting tumor growth in murine models. This research program will focus on two specific aims: Aim 1, synthesis and characterization of the molecules for EISA in the nuclei of mOS cells; Aim 2, pilot study of the EISA substrates for inhibiting mOS tumors in clinically relevant murine models. The rigor of prior research is that (i) overexpression of alkaline phosphatase (ALP) is a key feature of mOS, (ii) our preliminary results show that EISA forms NFs inside nuclei to selectively inhibit mOS cells, and (iii) EISA forms cytosolic NFs to selectively inhibit mOS tumors in vivo. The innovation is to target the nuclei of mOS cells by EISA. The success of the proposed studies will contribute to the development of new molecular targeting agents for selectively killing mOS, which may ultimately lead to breakthrough in treating mOS.


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	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	2	12/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	2	7/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $81,250 )
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	2	7/18/2022	NON-COMPETING CONTINUATION	$81,250
														Subtotal = $81,250

Issue Date FY: 2021 ( Subtotal = $81,250 )
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	1	7/9/2021	NEW	$81,250
														Subtotal = $81,250

Grand Total All Awards = $162,500

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Testing in-situ formed nanofibers for inhibiting metastatic osteosarcoma (mOS) in murine models

Award Number: R03CA262920

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/09/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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