# The development of novel radiation-sensitizer based on ultra-small carbon dots

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $507,058

## Abstract

Abstract
 Diagnosed in >187,000 persons each year, non–small cell lung carcinoma (NSCLC) has been a leading
cause of cancer-related mortality in the US. For NSCLC patients, radiation therapy (RT) or chemoradiotherapy
has been used as the standard care when the disease stays at locally advanced or local regional stage. Recently,
radiotherapy have also been proven to be a viable alternative to lobectomy and lymph node dissection in stage
I NSCLC patients. Despite its wide application in NSCLC patient management, the efficacy of RT would often
be limited by the innate or acquired radioresistance. A wide range of radiosensitizers, such as cisplatin, 5-Fu,
nicotinamide, and etoposide, are often used in concurrent with RT to improve treatment outcome. Unfortunately,
these drugs could also cause severe systematic toxicities while enhancing tumor killing efficacy.
 This research proposes to develop a new category of radiosensitizer based on the ultra-small metal-
intercalated-carbon dots (named as M@Cdots), aiming to achieve enhanced cancer killing effect with minimal
systemic toxicity. Our M@Cdots have various unique features including: 1) enhanced RT therapy effects of X-
ray: the metal fillings of M@Cdots enhance photoelectric effects of X-ray, which, in conjunction with the carbon
surface catalyzed radiolysis, lead to remarkable radiosensitizing effects; 2) limited cytotoxicity: due to the bio-
inert carbon shell, M@Cdots are not susceptible to metal falloff as many conventional high-Z nanoparticles are,
and they cause little cytotoxicity in the absence of ionizing irradiation. Meanwhile, due to its ultra-small size (3nm),
M@Cdots are efficiently excreted through renal clearance with minimal reticuloendothelial system (RES) uptake,
reducing the risk of long-term toxicity to the host. 3) template synthesis methods: M@Cdots are made through
mesoporous template calcination and are 3 nm in diameter. This unique approach allows easy scale-up
synthesis of particles, and permits reliable metal encapsulation without extensively re-exploring synthetic
procedures.
 Our preliminary therapy results are very promising. On this basis, we will also explore active tumor targeting
by conjugating neurotensin (NTS) ligands to the surface of M@Cdots. The target, neurotensi receptor 1 (NTSR1),
is upregulated in large numbers of lung cancer patients but not in normal lung tissues. It is hypothesized that
with excellent tumor selectivity, efficient radiosensitization, minimal metal falloff, and efficient renal clearance,
NTS-M@Cdots will lead to greatly improved RT outcomes at the same or even reduced radiation doses while
causing minimal systemic toxicities. Although the current study is focused on NSCLC, the methodology can also
be easily extended to treatment of other cancer types, for instance head and neck, breast, and prostate cancer.

## Key facts

- **NIH application ID:** 10213674
- **Project number:** 5R01CA247769-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Zibo Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $507,058
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213674

## Citation

> US National Institutes of Health, RePORTER application 10213674, The development of novel radiation-sensitizer based on ultra-small carbon dots (5R01CA247769-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213674. Licensed CC0.

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