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In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano\u2010enabled drug delivery hydrogel platform. The platform utilizes \u201cPLGA\u2010PEG\u2010PLGA\u201d, an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature\u2010sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual\u2010loaded liposomes containing a first\u2010line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti\u2010apoptotic Bcl\u20102 pathway, ABT\u2010737. In vitro and in vivo evaluations demonstrate successful Bcl\u20102 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.<\/jats:p>","DOI":"10.1002\/smll.202310340","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T15:00:23Z","timestamp":1709910023000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo"],"prefix":"10.1002","volume":"20","author":[{"given":"Jiahui","family":"Zhu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology  Beijing 100190 China"},{"name":"School of Pharmacy and Bioengineering Chongqing University of Technology  Chongqing 400054 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