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However, achieving strong, stable, and predictable NIR emission remains a major challenge due to the complex interplay between quantum confinement, surface states, and structural modifications. From a synthesis standpoint, leveraging well-defined molecular precursors, precisely controlled heteroatom doping, and defect engineering provides a systematic approach to modulate emissive centers and achieve reproducible, high-performance NIR fluorescence. This review unravels the hidden balance between these governing factors and provides a unified mechanistic perspective on how sp2\/sp3 domain engineering, heteroatom doping, defect modulation, and donor\u2013acceptor interactions collectively dictate long-wavelength emission. The synthetic routes ranging from top-down to bottom-up approaches have been discussed comprehensively to highlight how precursor chemistry, reaction environment, and postsynthetic processing influence the electronic structure and photophysical behavior of CDs. Despite significant progress in optimizing the functionality of CDs, key barriers, including inconsistent synthesis, unresolved emission mechanisms, and limited translational readiness, continue to hinder clinical deployment. By bridging fundamental photo physics with emerging biomedical and optoelectronic applications, this review outlines critical design principles and future directions for the rational development of next-generation NIR-emissive CDs.<\/jats:p>","DOI":"10.1021\/cbmi.5c00234","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:19:32Z","timestamp":1770884372000},"page":"1214-1247","source":"Crossref","is-referenced-by-count":19,"title":["Unraveling the Hidden\nBalance between Quantum Confinement\nand Structural Modifications in Near-Infrared Fluorescent Carbon Dots"],"prefix":"10.1021","volume":"4","author":[{"given":"Muhammad","family":"Madni","sequence":"first","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zia","family":"Ullah","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shenzhen Children\u2019s Hospital , , , ,","place":["Shenzhen, Guangdong, China, 518038"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhilik","family":"Roy","sequence":"additional","affiliation":[{"name":"Jadavpur University , , ,","place":["Kolkata, India, 700032"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Yan","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Jin","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihao","family":"Wu","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuante","family":"Lan","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital of Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei, China, 050000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-3229","authenticated-orcid":true,"given":"Shubham","family":"Roy","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-0644","authenticated-orcid":true,"given":"Bing","family":"Guo","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]},{"name":"Harbin Institute of Technology , , ,","place":["Shenzhen, China, 518055"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"12","key":"2026090713153616300_cit1","doi-asserted-by":"publisher","first-page":"6130","DOI":"10.1021\/cr200359p","article-title":"Chemistry, biology, and medicine\nof fluorescent nanomaterials and related systems: new insights into\nbiosensing, bioimaging, genomics, diagnostics, and therapy","volume":"114","author":"Yao","year":"2014","journal-title":"Chem. 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