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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.<\/jats:p>","DOI":"10.1021\/acsami.6c14869","type":"journal-article","created":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T14:01:43Z","timestamp":1786284103000},"page":"43845-43855","source":"Crossref","is-referenced-by-count":0,"title":["NIR-Activated Enteric Prodrug Microparticles for Bioimaging-Guided Chemotherapy of Colorectal Cancer"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5298-0085","authenticated-orcid":true,"given":"Lei","family":"Zhou","sequence":"first","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Fei","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luya","family":"Zhu","sequence":"additional","affiliation":[{"name":"Southeast University , , ,","place":["Nanjing, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Southeast University , , ,","place":["Nanjing, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Duan","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0439","authenticated-orcid":true,"given":"Wenying","family":"Zhong","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University , , ,","place":["Nanjing, China, 211198"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-9241","authenticated-orcid":true,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Southeast University , , ,","place":["Nanjing, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"issue":"3","key":"2026090317185847400_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2022","journal-title":"CA Cancer J. 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