Fabrication of folate-decorated bafilomycin-loaded gold-coated MOF inhibits autophagy in cervical cancer cells for improving photothermal therapy
摘要
Photothermal therapy (PTT) demonstrates significant potential as a cancer treatment; however, the protective autophagy triggered by PTT limits its effectiveness. This study fabricated multifunctional nanoplatforms, BM/GNPs@ZIF8 (BGZ), by concurrently coating the autophagy inhibitor bafilomycin (BM) and the photothermal agent gold nanoparticles (GNPs) in the ZIF8 using the "one-pot method." Subsequently, a targeted alteration was performed using folic acid (FA) to develop FA-BM/GNPs@ZIF8 (FA-BGZ). The co-delivery of BM and GNPs aims to integrate autophagy regulation with PTT in a synergistic manner. The final NPs, FA-BGZ, integrate pH responsiveness, PTT, and tumor-target abilities. The stability is markedly enhanced after coating with ZIF8 (GNPs@ZIF8), with minimal effect on photothermal performance. The FA-BGZ exhibits a photothermal significant impact of approximately 32.74%. Concurrent coating of BM can inhibit autophagy and interfere with cancer cells' defensive mechanisms. Additional in vitro biological experiments further validate that FA-BGZ exhibits a significant cytotoxic effect on cervical cancer SiHa cells under near-infrared (NIR) exposure (IC50: 16.52 ± 3.48 μg/mL), decreasing mitochondrial membrane potential (MMP), and increasing reactive oxygen species (ROS), which subsequently leads to cell apoptosis. These findings suggest that FA-BGZ is a promising nanodrug delivery system (NDDS) that could enhance synergistic treatment approaches in cervical cancer cells.