Photosensitizing Nanoconstructs for Regulation of ATP-Binding Cassette Transporters in the Brain

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The adenosine triphosphate (ATP) molecule is the nucleotide of intracellular energy transfer. ATP is able to store and transport chemical energy within cells. Energy is released by hydrolysis of the third phosphate group, and this energy is captured by proteins to drive cellular processes. ATP-binding cassette (ABC) transporters are proteins found within our cells that take toxic chemicals from the inside of a cell and push them to the outside of a cell. Blood vessel cells in the brain adopt this protective mechanism to pump a variety of drugs out of the brain, thereby making treatment ineffective. There are currently no effective strategies for selective inhibition of ABC transporters in diseased tissues while sparing healthy tissues. This project fills a major gap by studying the fundamental mechanisms by which light, chemistry, and nanomaterials can be exploited to modulate ABC transporters in brain microvascular endothelial cells. This work will quantify the impact of photochemistry and nanomaterials on the activity and integrity of ABC transporters. Compartmentalization and spatial organization of photosensitizers in nanoscale objects will be investigated to alter or even enhance the photochemical effects on ABC transporters. A correlation between the photochemical modulation of organelles and the function of ABC transporters will also be established. The third objective of the project involves understanding how light modulates drug transport across the blood-brain barrier. The results of this project may enable the development of new types of nanoconstructs, which will enable a transformation in the treatment of brain cancer and other types of cancer. The proposed research will be seamlessly integrated with educational, mentoring, and outreach activities to advance the cross-disciplinary program in the field of Biophotonics and Neuroscience. The research results will be disseminated broadly through journal publications, conferences, and workshops held at UMD. This work will be presented at international conferences on photochemistry, photobiology, and biomedical optics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.