# Site Specific Drug Delivery with Light-responsive Conjugates for Photo-biomodulation

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $343,252

## Abstract

Project Summary/ Abstract
Light is an exceptional tool in disease treatment, offering precise controllability in treatment time and location.
Unlike UV light, longer visible and near infrared (IR) light is not toxic and reaches deeper tissues than UV for
clinical applications. However, chemical linkers that are cleavable by such biocompatible light are very scarce.
Long term goals are to develop chemical linkers that are cleaved by visible and near IR light for light-controlled
drug delivery, and to design and synthesize chemical conjugates that are used for pho-biomodulation. In the
previous project, a drug conjugate platform and photo-release strategy for site specific drug delivery were
established. Click and photo-unclick chemistry was demonstrated, where singlet oxygen (SO)-cleavable linker
is synthesized via amine-yne click reaction and cleaved by SO. The drug conjugates are composed of drug, SO-
cleavable linker, photosensitizer and cancer-targeting group. When illuminated with red light (690 nm), the
conjugates generate SO and release drug only in the illuminated region and treat the disease locally. In the next
5 years, a bolder photo-biomodulation strategy will be established using the light-responsive drug conjugate
platform. Overarching hypothesis is that local photo-biomodulation using visible and near IR light-responsive
conjugates can make systemic pharmacological effects via activation of immune system. Main goals in this
application are to design and prepare SO-cleavable conjugates of immunostimulant drugs and to prove that this
visible-light responsive conjugates can be used for generating systemic and tumor-specific anticancer effects.
The conjugates are activated by a focused local illumination, release drugs site-specifically, and stimulate
immune system to trigger systemic and tumor-specific immune responses. The systemic antitumor effect is
further enhanced by the combination with systemically administered drugs with non-overlapping mechanisms
with the local photo-biomodulation. The goals are realized with 3 specific aims: (1) Design and prepare SO-
activatable conjugates of immune-stimulating drugs and determine systemic antitumor effects, (2) Determine the
mechanisms of systemic effects of the photo-biomodulation and establish the immuno-pharmacodynamics, (3)
Determine the enhanced systemic antitumor effect of the local photo-biomodulation by adding clinically available
checkpoint inhibitors. Pharmacokinetic and immune-pharmacodynamic modeling is used for analyzing and
simulating dynamic changes of conjugates, released drugs, and immune cells in various tissues to gain
mechanistic insight at the systemic level. Major deliverables are (i) red-light responsive conjugates of
immunostimulant drugs, (ii) immune-pharmacodynamic models following photo-biomodulation, and (iii) validation
of our local photo-biomodulation for systemic effects. The strategy is tested using breast and colon cancer animal
models but it could be applic...

## Key facts

- **NIH application ID:** 10894762
- **Project number:** 5R01GM113940-09
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Youngjae You
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $343,252
- **Award type:** 5
- **Project period:** 2015-03-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894762

## Citation

> US National Institutes of Health, RePORTER application 10894762, Site Specific Drug Delivery with Light-responsive Conjugates for Photo-biomodulation (5R01GM113940-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894762. Licensed CC0.

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