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To address these challenges, we engineered a tumor-targeted nanoprobe (cRGD@ICN) by encapsulating ICG within a calcium carbonate (CaCO3) core, followed by surface functionalization with phospholipids and cyclic RGD (cRGD) peptides. The CaCO3 encapsulation enhanced ICG photostability and amplified NIR-II emission by 9.21-fold relative to free ICG. Meanwhile, cRGD conjugation enabled active targeting of integrin \u03b1v\u03b23, a receptor overexpressed on diverse tumor types. cRGD@ICN showed receptor-mediated endocytosis with specific uptake in HCT116, 4T1, and U87 cells in vitro, along with selective accumulation in human ex vivo colorectal cancer tissues. In vivo NIR-II fluorescence imaging revealed that cRGD@ICN achieved high-contrast tumor monitoring with a signal-to-background ratio (SBR) of 6.54 at 16 h postinjection in HCT116 tumor-bearing mice\u2500markedly outperforming the nontargeted control. More importantly, it also exhibited remarkable tumor-targeting ability across other tumor models (U87, 4T1). With precise tumor imaging, we performed real-time NIR-II fluorescence-guided resection of colorectal tumors, confirmed by the absence of residual tumor in the surgical cavity by H&amp;E analysis. Moreover, primary biosafety assessments confirmed favorable biocompatibility. This work provides a promising strategy to transform ICG into a high-performance NIR-II fluorescent nanoprobe and offers a potential approach for precision image-guided oncologic surgery.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02041","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:01:51Z","timestamp":1787158911000},"page":"24909-24920","source":"Crossref","is-referenced-by-count":1,"title":["cRGD-Functionalized\nCalcium Carbonate Nanoprobe for\nEnhanced NIR-II Fluorescence Imaging and Tumor-Targeted Navigation"],"prefix":"10.1021","volume":"98","author":[{"given":"Lenan","family":"Wang","sequence":"first","affiliation":[{"name":"Nankai University , , Tongyan Road, Haihe Education Park , ,","place":["Tianjin, China, 300350"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Nankai University , , Tongyan Road, Haihe Education Park , ,","place":["Tianjin, China, 300350"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8465-3997","authenticated-orcid":true,"given":"Zhaorui","family":"Song","sequence":"additional","affiliation":[{"name":"Bohai Rim Advanced Research Institute for Drug Discovery , , , ,","place":["Yantai, Shandong, China, 264117"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifan","family":"Wu","sequence":"additional","affiliation":[{"name":"Nankai University , , Tongyan Road, Haihe Education Park , ,","place":["Tianjin, China, 300350"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Cui","sequence":"additional","affiliation":[{"name":"Nankai University , , Tongyan Road, Haihe Education Park , ,","place":["Tianjin, China, 300350"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhong","family":"Dong","sequence":"additional","affiliation":[{"name":"Bohai Rim Advanced Research Institute for Drug Discovery , , , ,","place":["Yantai, Shandong, China, 264117"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9715-6292","authenticated-orcid":true,"given":"Meng","family":"Meng","sequence":"additional","affiliation":[{"name":"Nankai University , , Tongyan Road, Haihe Education Park , ,","place":["Tianjin, China, 300350"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin University, The Third Central Hospital of Tianjin , , 83 Jintang Road , Hedong, ,","place":["Tianjin, China, 300170"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4351-9186","authenticated-orcid":true,"given":"Qi","family":"Xin","sequence":"additional","affiliation":[{"name":"Tianjin University, The Third Central Hospital of Tianjin , , 83 Jintang Road , Hedong, ,","place":["Tianjin, China, 300170"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8177-9463","authenticated-orcid":true,"given":"Zhen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Bohai Rim Advanced Research Institute for Drug Discovery , , , ,","place":["Yantai, Shandong, China, 264117"]},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences , , ,","place":["Shanghai, China, 201203"]},{"name":"Nanjing University of Chinese Medicine , , ,","place":["Nanjing, China, 210023"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"5","key":"2026090306480868900_cit1","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/s41551-024-01275-7","article-title":"Molecular probes for in vivo optical imaging of immune cells","volume":"9","author":"Liu","year":"2025","journal-title":"Nat. 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