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NIR-Activated Enteric Prodrug Microparticles for Bioimaging-Guided Chemotherapy of Colorectal Cancer.

Created on 09 Aug 2026

Authors

Lei Zhou, Yue Fei, Ziyi Wang, Xiaohui Wang, Luya Zhu, Furong Zhao, Ni Duan, Yixuan Wang, Jing Wang, Wenying Zhong, Rui Wang

Published in

ACS applied materials & interfaces. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide. 5-Fluorouracil (5-FU) is a first-line chemotherapeutic widely used in CRC treatment, but its systemic administration often causes severe toxicity due to uncontrolled biodistribution. Herein, we present near-infrared (NIR)-activated enteric prodrug microparticles, HPMCP@L-UCNPs-ONB-5-FU, which enable spatiotemporally controlled release of 5-FU in the colon. The photocleavable prodrug o-nitrobenzyl-5-fluorouracil (ONB-5-FU) is conjugated to large upconversion nanoparticles (L-UCNPs) and encapsulated within the enteric polymer hydroxypropyl methylcellulose phthalate (HPMCP) to resist gastric degradation. After oral administration, low-power 980 nm excitation yields 800 nm emission for bioimaging, whereas high-power excitation generates strong 365 nm emission that cleaves the ONB linker and locally releases active 5-FU. In vitro studies confirmed light-gated and power-dependent drug release, while cellular and orthotopic CRC studies demonstrated potent tumor inhibition with minimal systemic toxicity. Overall, this work establishes a precise and biocompatible NIR-controlled prodrug activation paradigm for oral chemotherapy of CRC.

PMID:
42571659
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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