# Reducing Off-Target Accumulation of Chemotherapeutic Nanomedicines

> **NIH CA R01** · UNIVERSITY OF COLORADO DENVER · 2026 · $500,290

## Abstract

The work described in this proposal investigates a novel approach to reduce drug accumulation in healthy
tissues and improve the efficacy of chemotherapy. More specifically, we take advantage of recent studies
demonstrating an innate immune response (epithelial tightening) that limits viral infection, and our preliminary
data show that this response can be exploited to reduce the accumulation of nanoparticles in healthy tissues.
The key molecule involved in signaling the tightening response is IFN-λ, and we have shown that this cytokine
is produced in response to the injection of virus-like particles (lipoplexes). Moreover, pretreatment with this
cytokine elicits tightening in healthy tissues without affecting delivery to the tumor. We propose that eliciting this
response will permit unimpeded delivery to tumors under conditions where deposition in healthy tissues is
significantly reduced. As a demonstration of these effects, tumor-bearing mice pre-treated with IFN-λ exhibited
reduced accumulation of liposomal doxorubicin (Doxil®) in healthy organs, reduced toxicity, and improved
survival. By characterizing the tightening response in terms of IFN-λ dose, route of administration, and timing
as well as its effects on organ and skin toxicity, our experiments will identify conditions that can be used to
minimize adverse effects of chemotherapy while enhancing drug accumulation in the tumor. Finally, we will
explore the potential of utilizing the reduced accumulation in healthy tissues to more aggressively dose
chemotherapy in two syngeneic mouse models for ovarian cancer and conduct immune profiling to assess
synergistic effects of IFN-ʎ with Doxil.

## Key facts

- **NIH application ID:** 11291790
- **Project number:** 5R01CA289447-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** THOMAS  ANCHORDOQUY; Dmitri  Simberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $500,290
- **Award type:** 5
- **Project period:** 2025-03-01T00:00:00 → 2030-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11291790

## Citation

> US National Institutes of Health, RePORTER application 11291790, Reducing Off-Target Accumulation of Chemotherapeutic Nanomedicines (5R01CA289447-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/11291790. Licensed CC0.

---

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