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Despite the availability of multiple chemotherapeutic options, clinical efficacy remains limited due to poor drug solubility, restricted intestinal absorption, rapid systemic clearance, and multidrug resistance. Poly(lactic-co-glycolic acid) (PLGA), a well-established biodegradable and biocompatible copolymer, has gained significant attention for its potential in developing advanced drug delivery systems. Its tuneable degradation kinetics governed by the lactic-to-glycolic acid ratio enable precise modulation of drug release profiles. PLGA-based nanocarriers offer several therapeutic advantages, including improved solubility, extended colonic retention, and targeted delivery of anticancer agents. Furthermore, surface functionalization with copolymers, ligands, or stimuli-responsive moieties has demonstrated enhanced cellular uptake, tumor specificity, and cytotoxicity against CRC cells. This review highlights the recent developments in the synthesis, functional design, and biomedical application of PLGA nanocarriers in CRC treatment, emphasizing their role in overcoming key challenges such as chemoresistance and off-target toxicity. These advancements underscore the potential of PLGA-based polymeric systems in enhancing the therapeutic index and translational viability of anticancer therapies.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12943-025-02435-2","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T06:58:29Z","timestamp":1763017109000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Advances in PLGA-based polymeric nanocarriers for colorectal cancer therapy: overcoming chemoresistance through controlled delivery strategies"],"prefix":"10.1186","volume":"24","author":[{"given":"Mohammad Sakib","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urushi","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humood","family":"Al Shmrany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khang Wen","family":"Goh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Kesharwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"2435_CR1","first-page":"1","volume":"10","author":"S Shivshankar","year":"2025","unstructured":"Shivshankar S, Patil PS, Deodhar K, Budukh AM. 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