Multi-Bioinspired MOF Delivery Systems from Microfluidics for Tumor Multimodal Therapy

Abstract

Metal–organic framework (MOF)-based drug delivery systems have demonstrated values in oncotherapy. Current research endeavors are centralized on the functionality enrichment of featured MOF materials with designed versatility for synergistic multimodal treatments. Here, inspired by the multifarious biological functions including ferroptosis pattern, porphyrins, and cancer cell membrane (CCM) camouflage technique, novel multi-biomimetic MOF nanocarriers from microfluidics are prepared. The Fe3+, meso-tetra(4-carboxyphenyl)porphine and oxaliplatin prodrug are incorporated into one MOF nano-system (named FeTPt), which is further cloaked by CCM to obtain a “Trojan Horse”-like vehicle (FeTPt@CCM). Owing to the functionalization with CCM, FeTPt@CCM can target and accumulate at the tumor site via homologous binding. After being internalized by cancer cells, FeTPt@CCM can be activated by a Fenton-like reaction as well as a redox reaction between Fe3+ and glutathione and hydrogen peroxide to generate hydroxyl radical and oxygen. Thus, the nano-platform effectively initiates ferroptosis and improves photodynamic therapy performance. Along with the Pt-drug chemotherapy, the nano-platform exhibits synergistic multimodal actions for inhibiting cancer cell proliferation in vitro and suppressing tumor growth in vivo. These features indicate that such a versatile biomimetic MOF delivery system from microfluidics has great potential for synergistic cancer treatment.