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

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $228,335

## Abstract

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.

## Key facts

- **NIH application ID:** 10197928
- **Project number:** 5R21EB028508-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Huang Chiao Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $228,335
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197928

## Citation

> US National Institutes of Health, RePORTER application 10197928, Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier (5R21EB028508-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10197928. Licensed CC0.

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