# Project 1- Bioadhesive Sunscreens and Triplet-State Quenchers for Melanoma Prevention

> **NIH NIH P50** · YALE UNIVERSITY · 2020 · $521,465

## Abstract

PROJECT 1: PROJECT SUMMARY
Cancers that derive from skin cells comprise the most commonly diagnosed malignancies in the US, including
~76,000 cases of cutaneous malignant melanoma responsible for over $100M in healthcare costs and ~10,000
deaths annually. Ultraviolet radiation (UVR) exposure is the major environmental risk factor for melanoma
development; thus, limiting UVR exposure and its damaging effects is a logical strategy for melanoma
prevention. We hypothesize that early and fundamental processes of melanomagenesis can be inhibited via
complementary approaches that reduce both direct and indirect UVR-induced melanocyte genotoxicity. While
previous topical formulations have attempted to address direct damage pathways (using sunscreens) and
indirect damage pathways (using antioxidants), recent breakthroughs from our research programs provide us
with unique opportunities for further technological innovation in preventing malignant melanoma. We have
developed a novel sunscreen delivery platform for the prevention of UVR-damage that uses bioadhesive
nanoparticles (BNPs). UVR-absorbing compounds are stably encapsulated within particles that have a
biodegradable polymer core and a surface coating that allows them to adhere covalently to the stratum
corneum, increasing sunscreen agent efficiency and durability while mitigating safety concerns attributable to
penetration of agents into the epidermis, e.g. contact allergy, increased generation of ROS, and hormone
receptor binding. We have also identified a novel pathway of indirect damage that continues long after UVR-
exposure, via triplet-state electrons in melanin fragments that also drive formation of cyclobutane pyrimidine
dimers (CPDs). This process of chemiexcitation occurs over the course of hours, suggesting several
opportunities to prevent or dissipate the high energy excited states involved, by using agents that have not yet
been examined for this novel activity. Accordingly, we have demonstrated the potential of triplet-state
quenchers (TSQs) and triplet-state preventers (TSPs) to avert formation of these delayed CPDs. The overall
goal of this proposal is to systematically optimize these approaches for melanoma prevention. To accomplish
this, we will develop both a novel broad-spectrum BNP-sunscreen and a novel TSQ/TSP topical formulation
that, in combination, we hypothesize will provide optimized prevention of the direct and indirect UVR-induced
melanocyte genotoxicity that fundamentally drives melanomagenesis.

## Key facts

- **NIH application ID:** 9988372
- **Project number:** 5P50CA121974-13
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** MICHAEL GIRARDI
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $521,465
- **Award type:** 5
- **Project period:** 2006-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988372

## Citation

> US National Institutes of Health, RePORTER application 9988372, Project 1- Bioadhesive Sunscreens and Triplet-State Quenchers for Melanoma Prevention (5P50CA121974-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988372. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*