Wednesday, December 4, 2024 12/4/2024

Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier

Award Number: R21EB028508
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Most primary brain tumors are managed by maximal safe resection followed by chemotherapy and radiation to treat residual and potentially infiltrative tumor cells. However, these adjuvant approaches do not effectively treat the tumor-invaded brain regions due to an intact blood-brain barrier (BBB) that restricts efficient drug penetration or a high risk of toxicity to nearby neural structures. Increasing clinical evidence indicates that the strength of the BBB in protecting brain tumors from exposure to circulating drugs is maintained by not only the intact tight junctions between endothelial cells, but also a broad range of ATP-binding cassette (ABC) drug efflux transporters on endothelial and cancer cells. Our central hypothesis is that sub-cytotoxic photodynamic priming (PDP), which modulates both the tight junction proteins and ABC transporters, can offer a more specific and less disruptive strategy to deliver drugs into the brain tumor effectively. Leveraging cutting-edge nanotechnology, optical imaging and computational modeling, three specific aims will test our hypothesis using orthotopic patient-derived xenograft rat models of glioblastoma. Aim 1 will unravel the molecular impact of nanotechnology-assisted PDP on the tight junction proteins and ABC efflux transporters of brain endothelial cells and cancer cells. Aim 2 will employ fluorescence imaging to monitor nanomedicine delivery and establish a physiologically based pharmacokinetic model. Aim 3 will apply image-based pharmacokinetic modeling to guide the initiation of PDP for bidirectional modulation of drug transport in vivo. Creation of such a pipeline to translate fundamental discoveries into potential therapeutics stands to dramatically accelerate the paradigm shift from standard cytotoxic procedures to a gentler photochemical approach that will revolutionize glioblastoma treatment. The principles and nanotechnology developed here will be adaptable to understanding and treating a broad range of central nervous system disorders, such as neuro-degenerative malignancies and spinal cord disease.


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 = -$24 )
2025	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	10/25/2024	NON-COMPETING CONTINUATION	-$24
														Subtotal = -$24

Issue Date FY: 2022 ( Subtotal = $189,506 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	8/1/2022	NON-COMPETING CONTINUATION	$18,951
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	2/26/2022	NON-COMPETING CONTINUATION	$170,555
														Subtotal = $189,506

Issue Date FY: 2021 ( Subtotal = $228,335 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	5/26/2021	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/1/2021	NON-COMPETING CONTINUATION	$228,335
														Subtotal = $228,335

Issue Date FY: 2020 ( Subtotal = $203,530 )
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	6/18/2020	NEW	$203,530
														Subtotal = $203,530

Grand Total All Awards = $621,347

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Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier

Award Number: R21EB028508

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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