{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:11:41Z","timestamp":1779361901987,"version":"3.51.4"},"reference-count":121,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chondroitin sulfate (CS)-based nanoparticles have emerged as versatile and multifunctional platforms for cancer therapy, integrating effective drug delivery with diagnostic capabilities. Their ability to exploit the enhanced permeability and retention (EPR) effect enables selective accumulation within tumor tissues, while surface modification with CS enhances targeting efficiency through strong conformational and electrostatic affinity for CD44 receptors, which are overexpressed in many cancer cells. In addition, CS interacts with E-selectin, providing dual-targeting capabilities superior to those of other polysaccharides such as hyaluronic acid. A wide variety of CS-derived nanostructures\u2014including micelles, nanogels, hybrid liposomes, and CS\u2013drug conjugates\u2014have shown great potential not only in drug delivery but also in advanced therapeutic modalities such as photodynamic, sonodynamic, and immunotherapy. This review discusses recent advances (2020\u20132025) in CS-based nanoplatforms for cancer therapy, with particular emphasis on the role of CS within nanostructures. It highlights how the functionalization of nanoparticles with CS represents a powerful strategy to improve colloidal stability, pharmacokinetics, and receptor-mediated uptake, thereby enabling controlled, site-specific drug release and reducing off-target toxicity. Ultimately, these advances open new opportunities for cancer treatment, with the potential for bench-to-clinic translation through the integration of AI-guided design, organelle-specific targeting, multi-pathway modulation, and immune system engagement.<\/jats:p>","DOI":"10.3390\/molecules30244798","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:22:58Z","timestamp":1765905778000},"page":"4798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chondroitin Sulfate-Based Nanoplatforms: Advances and Challenges for Cancer Therapy"],"prefix":"10.3390","volume":"30","author":[{"given":"Ludovica","family":"Scorzafave","sequence":"first","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9592-1333","authenticated-orcid":false,"given":"Giuseppe","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-1963","authenticated-orcid":false,"given":"Fiore Pasquale","family":"Nicoletta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-0446","authenticated-orcid":false,"given":"Francesca","family":"Iemma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-0152","authenticated-orcid":false,"given":"Manuela","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Health and Nutritional Science, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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