Synthesis and Application of a Novel Multifunctional Nanoprodrug for Synergistic Chemotherapy and Phototherapy with Hydrogen Sulfide Gas

With the dilemma of limited efficacy of individual therapies, it is crucial to develop innovative combination therapy systems to target the complex pathogenesis of cancer. In this study, we designed a nanoprodrug ISL@MIL-101-ADT to facilitate synergistic delivery of hydrogen sulfide (H₂S) and prodrug ISL for specific eradication of tumor cells with minimal toxicity and maximal efficacy. The nanoprodrug passively targeted tumors through enhanced permeation and retention effects, followed by disintegration and release of IR780, lonidamine (LND), and H₂S. IR780 localizes LND to mitochondria to enhance therapeutic effects and turn on the phototherapy and chemotherapy when exposed to a laser; H₂S inhibits procancer signaling pathways and mitochondrial function. In vivo experiments have demonstrated that ISL@MIL-101-ADT exhibits excellent pharmacokinetic properties and significant tumor inhibitory effects. Additionally, this nanoprodrug possesses outstanding photothermal and fluorescence imaging capabilities. Therefore, we strongly believe that the nanoprodrug present herein holds great potential for application in cancer therapy.