A Light-Driven Electrochromic Materials-Based Nanomotor for HS-Controlled Drug Release in Synergistic Cancer Chemotherapy Immunotherapy.

Nanomotors hold tremendous potential for drug delivery. However, current nanomotors face limitations that compromise efficiency of drug utilization, including the use of inorganic materials with suboptimal soft interface and biocompatibility, uncontrollable drug release, insufficient directional control, and slow movement speeds. Herein, we present a novel near-infrared (NIR) light-driven porous unsymmetric nanomotor with ultrafast motion, which utilizes hydrogen sulfide (HS)-responsive cationic organic π-electron structure-based electrochromic material (F1) for the payload and controlled release of anionic anticancer drugs, enabling synergistic cancer chemotherapy and immunotherapy. We demonstrate that the nanomotor can precisely target tumors driven by thermophoresis, tumor-targeting peptide (RGD), and HS (highly expressed in tumors and acted as chemoattractants), which induces chemotactic behavior to guide nanomotors into tumors. Once in the tumors, the cationic F1 is reduced to the diene F2 upon reaction with HS, activating the nanomotor's NIR fluorescence for real-time monitoring of drug delivery and release in vivo. Upon exposure to HS, the nanomotor undergoes disassembly due to the disruption of electrostatic interactions between the anionic anticancer drugs and the cationic F1, leading to the precise and controlled drug release, ensuring uniform distribution across the tumor. This innovative strategy would open avenues for delivering mRNA vaccines or other anionic drugs.