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NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

Award Number: R01CA260855
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/04/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY - ABSTRACT The excitement about nanomedicine stems from the potential application of nanoscience to solve challenging medical problems. Inorganic nanoparticles (iNPs) exhibit unique properties that favor their diverse application in medicine, engineering, science, and technology. The large surface-to-volume ratio of these iNPs provides sites for the attachment of multiple drugs or imaging agents for therapy and imaging of diverse human diseases. Further conjugation of biological entities, such as proteins, nucleic acids, and lipids, confers specific targeting of these iNPs to desired tissues in vivo. Recent studies have shown that the intrinsic properties of some iNPs can be harnessed for therapeutic outcomes. Still, spontaneous stimulation of intrinsic therapeutic effects through interactions of the NPs with intracellular organelles, proteins, or molecular processes is difficult to control, leading to significant off-target toxicity. An alternative therapeutic approach is to transform some iNPs into nanoscale energy transducers. Quantum dots, upconversion NPs, carbon nanomaterials, and photocatalytic NPs are some nanoscale energy transducers that have shown promise in the treatment of human diseases. The excellent redox properties of these nanophotosensitizers offer high spatiotemporal control and precision phototherapy upon absorption of light. Two major limitations of current phototherapeutic interventions are the limited penetration of light used to activate the photosensitizers, which confines therapy to shallow lesions, and the frequent reliance on molecular oxygen to generate cytotoxic reactive oxygen species, a condition that precludes the effective treatment under the hypoxic conditions found in many solid and hematologic tumors. Recently, we developed radionuclide stimulated therapy that leverages the interaction of Cerenkov radiation emitting radionuclides to stimulate the production of reactive oxygen species from photosensitizers. The spatiotemporal therapeutic effects of these interactions allow the treatment of diverse diseases without tissue depth limitation that affects light-based therapies. Supported by new concepts grounded in robust preliminary data, we propose to (1) explore new nanostrategies to overcome the impediment to delivering NPs to tumors, (2) disrupt the protective interactions of cancer with stromal cells to enhance treatment response, and (3) exert sustainable therapeutic effect via multidimensional combination therapy to achieve disease-free survival. At the completion of this study, we would develop new nanoplatforms for the treatment and imaging of cancer and bone lesions.


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 = $675,432 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Detection and Diagnosis Research	000	9	7/21/2025	NON-COMPETING CONTINUATION	$675,432
														Subtotal = $675,432

Issue Date FY: 2024 ( Subtotal = $694,789 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Detection and Diagnosis Research	000	8	8/22/2024	NON-COMPETING CONTINUATION	$694,789
														Subtotal = $694,789

Issue Date FY: 2023 ( Subtotal = $717,592 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Detection and Diagnosis Research	002	7	8/2/2023	NON-COMPETING CONTINUATION	$717,592
2023	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Detection and Diagnosis Research	001	6	10/31/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$649,537
2023	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	000	5	10/31/2022	COMPETING CONTINUATION	-$649,537
														Subtotal = $717,592

Issue Date FY: 2022 ( Subtotal = $734,204 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Detection and Diagnosis Research	001	6	8/11/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$734,204
2022	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	000	5	8/11/2022	COMPETING CONTINUATION	$0
														Subtotal = $734,204

Issue Date FY: 2021 ( Subtotal = $708,514 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	000	5	8/4/2021	COMPETING CONTINUATION	$708,514
														Subtotal = $708,514

Grand Total All Awards = $3,530,531

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NANOPHOTOSENSITIZERS FOR REGENERATIVE PHOTOTHERAPY

Award Number: R01CA260855

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/04/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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