GSH-responsive Pt-based nanomotor with improved doxorubicin delivery for synergistic osteosarcoma chemotherapy

Osteosarcoma (OS), a highly malignant primary tumor, poses significant threats. Chemotherapy remains the main treatment approach but is limited by low drug bioavailability, poor permeability, and notable side effects. Herein, a near-infrared light (NIR)-driven and GSH-responsive poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor, wherein disulfide bonds served as GSH sponsors and platinum nanoparticles as producers of reactive oxygen species (ROS) to induce cell apoptosis, combined with NIR-driven propulsion to enhance the inhibitory effect of encapsulated doxorubicin (DOX). The results demonstrated that the PSPDP nanomotor can be effectively driven due to its good photothermal properties, with its movement speed increased 2.10 times under NIR laser exposure. Additionally, the efficiency of DOX release increased with the increase in GSH concentration, demonstrating favorable GSH responsiveness. Pt-NPs also exhibited good photothermal properties, enabling self-thermophoresis to drive. Minimal cytotoxic effects of PSPDP were observed on a series of cell lines compared with DOX solution and Pt-NPs. Notably, the Pt-NPs generated a significant amount of ROS, synergistically enhancing the therapeutic effect of DOX, as evidenced by a 5.53-fold increase in OS cell growth inhibition and evident osteosarcoma growth inhibition in the nude mice model. Thus, the NIR-driven, localized, and low-toxic nanomotor may offer a promising therapeutic strategy for OS intervention. STATEMENT OF SIGNIFICANCE: Enhancing drug penetration efficiency and developing delivery systems that respond to the tumor microenvironment to release drugs are effective strategies for treating osteosarcoma (OS). Here, a near-infrared (NIR) light-driven and glutathione (GSH)-responsive nanomotor, integrating poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP), was produced and used for OS treatment. This PSPDP nanomotor exhibits significant advancements in photothermal activation and self-thermophoresis, enabling a 2.10-fold increase in movement speed under NIR exposure. Such enhanced motility improves the localized delivery and controlled release of doxorubicin, thus increasing drug bioavailability and minimizing systemic toxicity. Additionally, the nanomotor's ability to generate reactive oxygen species significantly amplifies its therapeutic impact, evidenced by a remarkable 5.53-fold increase in tumor growth inhibition. These features make the PSPDP nanomotor a promising candidate for effective and targeted OS treatment strategies.