Tuesday, July 1, 2025 7/1/2025

Subcellular enzyme-instructed self-assembly for molecular anticancer nanomedicines

Award Number: R01CA142746
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/08/2010
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Subcellular enzyme-instructed self-assembly for molecular anticancer nanomedicines - ABSTRACT Despite the progress in molecular therapy and immunotherapy, multiple underlying cellular mechanisms cause resistance to cancer therapy. There are urgent needs to develop innovative approaches to meet these challenges. The proposed study is to develop subcellular enzyme-instructed self-assembly (sEISA), which includes mitochondrial EISA (mitoEISA) and cytoplasmic EISA (cytoEISA), for generating molecular nanofibers to overcome drug resistance and immunosuppression in cancer therapy. Our preliminary studies have shown that sEISA selectively targets the mitochondria of cancer cells and minimizes drug resistance. Most importantly, our preliminary study shows that sEISA inhibits the growth of immunosuppressive tumors in vivo. Thus, we propose to further develop sEISA against drug resistant cancer cells and tumors. The proposed research has three specific aims: Aim 1, developing mitoEISA for selectively targeting cancer cells; Aim 2, developing cytoEISA for minimizing drug resistance and immunosuppression; and Aim 3, evaluating sEISA in ovarian cancer xenograft murine models. The central hypothesis is that sEISA spatiotemporally generates molecular nanofibers, which interact with multiple cellular proteins and interrupt multiple cellular processes inside cancer cells to minimize drug resistance. Our preliminary results support the central hypothesis. The innovation is that the mechanisms of the action of the molecular nanofibers significantly depart from the ligand-receptor dogma of the current anticancer drugs. The long-term goal of the proposed work is to develop sEISA to generate molecular nanofibers for overcoming resistance in cancer therapy. We anticipate that this research will provide innovative anticancer approaches to address the problems of drug resistance and immunosuppression in cancer therapy, thus ultimately will improve the survivorship of cancer patients.


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: 2025 ( Subtotal = $397,052 )
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	15	5/1/2025	NON-COMPETING CONTINUATION	$357,346
2025	2025	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	15	5/23/2025	NON-COMPETING CONTINUATION	$39,706
														Subtotal = $397,052

Issue Date FY: 2024 ( Subtotal = $579,612 )
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	14	2/5/2024	NON-COMPETING CONTINUATION	$549,107
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	14	3/28/2024	NON-COMPETING CONTINUATION	$0
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	002	14	4/24/2024	NON-COMPETING CONTINUATION	$30,505
														Subtotal = $579,612

Issue Date FY: 2023 ( Subtotal = $397,052 )
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	003	13	7/10/2023	NON-COMPETING CONTINUATION	$0
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	002	13	4/12/2023	NON-COMPETING CONTINUATION	$397,052
2023	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	12	10/24/2022	SUPPLEMENT FOR EXPANSION	$0
2023	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	12	3/28/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $397,052

Issue Date FY: 2022 ( Subtotal = $691,505 )
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	005	12	9/22/2022	SUPPLEMENT FOR EXPANSION	$228,691
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	004	12	5/3/2022	SUPPLEMENT FOR EXPANSION	$73,705
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	003	12	4/29/2022	NON-COMPETING CONTINUATION	$389,109
2022	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	002	11	4/19/2022	COMPETING CONTINUATION	$0
2022	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	11	10/12/2021	COMPETING CONTINUATION	$783
2022	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	10	10/12/2021	NON-COMPETING CONTINUATION	-$783
														Subtotal = $691,505

Issue Date FY: 2021 ( Subtotal = $468,559 )
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	11	9/23/2021	SUPPLEMENT FOR EXPANSION	$51,237
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	11	3/9/2021	COMPETING CONTINUATION	$417,322
														Subtotal = $468,559

Issue Date FY: 2019 ( Subtotal = $357,100 )
2019	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	10	8/1/2019	NON-COMPETING CONTINUATION	$357,100
														Subtotal = $357,100

Issue Date FY: 2018 ( Subtotal = $368,145 )
2018	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	9	7/27/2018	NON-COMPETING CONTINUATION	$368,145
														Subtotal = $368,145

Issue Date FY: 2017 ( Subtotal = $368,145 )
2017	2017	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	8	8/7/2017	NON-COMPETING CONTINUATION	$368,145
														Subtotal = $368,145

Issue Date FY: 2016 ( Subtotal = $368,145 )
2016	2016	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Cancer Treatment Research	000	7	8/3/2016	NON-COMPETING CONTINUATION	$368,145
														Subtotal = $368,145

Issue Date FY: 2015 ( Subtotal = $383,751 )
2015	2015	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Cancer Treatment Research	001	6	9/25/2015	COMPETING CONTINUATION	$383,751
2015	2014	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Cancer Treatment Research	000	5	9/22/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,751

Issue Date FY: 2014 ( Subtotal = $308,474 )
2014	2014	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Cancer Treatment Research	000	5	1/16/2014	NON-COMPETING CONTINUATION	$286,214
2014	2014	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Cancer Treatment Research	001	5	4/21/2014	NON-COMPETING CONTINUATION	$22,260
														Subtotal = $308,474

Issue Date FY: 2013 ( Subtotal = $298,934 )
2013	2013	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	4	1/28/2013	NON-COMPETING CONTINUATION	$143,107
2013	2013	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	4	6/28/2013	NON-COMPETING CONTINUATION	$155,827
														Subtotal = $298,934

Issue Date FY: 2012 ( Subtotal = $318,015 )
2012	2012	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	3	3/8/2012	NON-COMPETING CONTINUATION	$318,015
														Subtotal = $318,015

Issue Date FY: 2011 ( Subtotal = $318,015 )
2011	2011	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	2	1/24/2011	NON-COMPETING CONTINUATION	$295,065
2011	2011	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	001	2	5/13/2011	NON-COMPETING CONTINUATION	$22,950
														Subtotal = $318,015

Issue Date FY: 2010 ( Subtotal = $327,850 )
2010	2010	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Cancer Treatment Research	000	1	2/8/2010	NEW	$327,850
														Subtotal = $327,850

Grand Total All Awards = $5,950,354

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Subcellular enzyme-instructed self-assembly for molecular anticancer nanomedicines

Award Number: R01CA142746

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/08/2010

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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