MnMOF-based microwave-glutathione dual-responsive nano-missile for enhanced microwave Thermo-dynamic chemotherapy of drug-resistant tumors

Abstract

Metal-organic frameworks (MOFs) have been developed for tumor therapy in recent years, but so far there have been very few reports about the use of single metallic manganese (Mn) MOF in tumor therapy due to limited types of organic ligands. Expending on advantages of Mn-based nanoplatform, a novel magnetic resonance imaging (MRI)-monitored, microwave (MW) thermo-dynamic sensitized, and glutathione (GSH)-responsive Mn-based MOF is nano-engineered by combining imidazole containing sulfhydryl bond with Mn2+ for cisplatin (CDDP) loading, the phase-changing material (PCM) and tumor cell membrane (TCM) with homologous targeting are modified to finally generate MnMOF-CDDP@PCM-TCM nano-missile (TMCP Nm). Through active and passive targeting, MW-GSH dual-response, and site-directed release, the nano-missile can effectively reverse CDDP resistance, amplify the efficacy of MW thermo-dynamic chemotherapy, and finally achieve excellent therapeutic effect on drug-resistant tumor models both in vivo and in vitro. This strategy differs from traditional chemotherapy and MW thermotherapy (MWT), which triggers a series of changes in the tumor microenvironment that make subsequent chemotherapy more effective. In this study, a novel Mn-based MOF is designed and synthesized, which opens a new way to solve the problem of drug-resistance caused by chemotherapeutic drugs represented by CDDP in tumor therapy, and will greatly expand the application of MOFs and chemotherapeutic drugs.