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.