Metal-Organic Frameworks@Thermosensitive Hydrogel as Injectable Implant for Dual Drug Synergistic Oral Cancer Therapy

Local cancer therapy with multiple drugs has emerged as a novel therapeutic approach for facilitating the sustained delivery of therapeutic molecules that effectively suppress tumor growth. In this study, we developed a hybrid nanocomposite in which metal-organic frameworks (MOFs) were integrated with thermosensitive hydrogels to devise an injectable implant. Doxorubicin (Dox) and celecoxib (Cel) were coloaded into the system for localized oral cancer therapy (Dox/Cel/MOFs@Gel). This medical platform exhibited a high capacity for drug loading, steady and pH-responsive release of dual drugs, and enhanced toxic effects against oral cancer cells (KB and SCC-9) in vitro. The nanocomposites displayed outstanding tumor inhibition efficacy in vivo, inducing tumor apoptosis and regulating tumor angiogenesis due to the synergistic effects of Dox and Cel. It was found that this local treatment resulted in considerably lower systemic toxicity and no apparent injury to the other organs. The biocompatibility test of the MOFs that constructed the nanocomposite indicated reasonable biosafety in vivo as no evidence of persistent toxicity was observed. The results of this study demonstrate that the injectable nanocomposite (Dox/Cel/MOFs@Gel) possesses unique biological abilities in terms of pH-responsiveness, antitumor efficacy, and biocompatibility, suggesting that the nanocomposite is a promising vehicle for local oral cancer treatment.