A multifunctional MOF-based nanohybrid as injectable implant platform for drug synergistic oral cancer therapy

摘要

Toward eradicating tumor, it is crucial to facilitate the sustained delivery of encapsulated drugs and render enhancements of therapeutic effectiveness. Local cancer therapy with combined drugs has emerged as a promising therapeutic strategy. Herein, we put forward to construct 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). In view of the antiangiogenetic activity of Cel, Cel was in alliance with Dox in order to improve treatment efficacy. The particle size, morphological characterization from SEM and TEM, stability, drug loading efficiency, drug release behaviors in vitro of Dox/Cel/MOFs@Gel were examined. The efficacy of Dox/Cel/ MOFs@Gel in oral cancer cell lines as well as cell internalization was evaluated. 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 indicated reasonable biosafety as no evidence of persistent toxicity in vivo was observed. The injectable nanocomposite (Dox/Cel/MOFs@Gel) possesses unique biological abilities in terms of pH-responsiveness, antitumor efficacy, biocompatibility, and simultaneously release hydrophobic and hydrophilic drug at the oral tumor site, suggesting that this nanocomposite is a promising vehicle for local oral cancer treatment.