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Existing reviews on hydrogel-based CRC treatments mainly focus on synthetic materials or single-responsive systems concerning drug loading and local delivery. Natural polysaccharides possess inherent anti-inflammatory, antioxidant and antitumor activities, and polysaccharide hydrogels (PSHs) prepared from them exhibit favorable biocompatibility, tunable structures and potential targeting capability, which can synergistically enhance the efficacy of loaded drugs and thus become a research hotspot. This article summarizes the pathogenesis and conventional treatments of CRC, introduces monocomponent and composite PSHs as well as physical and chemical crosslinking methods, and emphasizes their tumor microenvironment (TME)-responsive mechanisms, combined drug effects and clinical applications. It also analyzes the challenges in safety evaluation and practical application, and summarizes recent advances in the use of artificial intelligence (AI) for PSHs design, regulation, performance prediction and implementation. This paper serves as a reference for follow-up research and clinical translation of hydrogels prepared from natural polysaccharides for the treatment of CRC.<\/jats:p>","DOI":"10.3390\/gels12070590","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:52:24Z","timestamp":1783007544000},"page":"590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Research Progress on Natural Polysaccharide Hydrogels in the Diagnosis and Treatment of Colorectal Cancer"],"prefix":"10.3390","volume":"12","author":[{"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafei","family":"Long","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqiao","family":"Zha","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyi","family":"Zhuang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanhua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pharmaceutical Research for Tumor Prevention and Treatment, Department of Education of Guizhou Province, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlei","family":"Guo","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, No. 34 Nanshan Road, Nan\u2019an District, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-1766","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zunyi Medical University, Zunyi 563000, China"},{"name":"Guizhou Key Laboratory of Modern Traditional Chinese Medicine Creation, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1146\/annurev-pathmechdis-031521-041113","article-title":"Metabolism and Colorectal Cancer","volume":"18","author":"Sedlak","year":"2023","journal-title":"Annu. 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