# Development of a radiation-activatable nanoparticle for lung cancer therapy

> **NIH NIH R41** · ATHNA BIOTECH, INC. · 2021 · $400,000

## Abstract

ABSTRACT
Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality. NSCLC accounts for 85% of
all lung cancers, and is diagnosed in 234,030 persons each year in the US. For the majority of patients with
locally advanced or local regional disease, radiation therapy (RT) is the standard care. However, the dose and
efficacy of RT is limited by normal tissue toxicity. To improve tumor control, radiosensitizers such as cisplatin
and paclitaxel are used in concurrent with RT, i.e. chemoradiotherapy (CRT). However, CRT is associated with
high levels of acute and systemic toxicity. Many patients are unfit to receive CRT or complete the planned
courses. There is an urgent need of methodologies that can deliver radiosensitizers site-specifically to tumors to
enhance RT.
Athna Biotech, Inc. is developing a new CRT approach where radiation is utilized to locally activate systemically
delivered therapeutics. Specifically, we have synthesized a radiation-responsive prodrug, DM1-NO, a
nitrosylated maytansinoid DM1. The prodrug can be loaded into poly(lactide-co-glycolic)-block-poly(ethylene
glycol) nanoparticles and delivered to tumors. To improve delivery efficiency, the nanoparticles are conjugated
with NTSmut, a ligand that has high affinity towards NTSR1, which is up-regulated in 59.7% lung tumors. During
RT, irradiation elevates oxidative stress in tumors, resulting in the disassociation of DM1-NO and the release of
DM1 and nitric oxide (NO). Both DM1 and NO are effective radiosensitizers, working synergistically to enhance
RT. With nanoparticle delivery, NTSR1 targeting, conformal radiation, and radiation-responsive activation, this
approach is associated with high tumor selectivity thus permitting accurate radiosensitization. The methodology
can be extended to treatment of other cancers, such as prostate, head and neck, breast, and colon cancer,
where NTSR1 is also upregulated.

## Key facts

- **NIH application ID:** 10259278
- **Project number:** 1R41CA257584-01A1
- **Recipient organization:** ATHNA BIOTECH, INC.
- **Principal Investigator:** Zhi Liu
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2021-06-14 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259278

## Citation

> US National Institutes of Health, RePORTER application 10259278, Development of a radiation-activatable nanoparticle for lung cancer therapy (1R41CA257584-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10259278. Licensed CC0.

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