GSH-responsive Pt-based nanomotor with improved doxorubicin delivery for synergistic osteosarcoma chemotherapy
Sheng Xu1, Ziwei Hu2, Weihao Zheng2
1Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; Life Sciences Institute, Guangxi Medical University, Nanning 530021, China.
Abstract:
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.
Insights
A novel nanomotor effectively treats osteosarcoma by using near-infrared light to enhance drug delivery and release. This targeted approach increases therapeutic efficacy and reduces side effects for osteosarcoma (OS) intervention.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Osteosarcoma (OS) is a malignant tumor with limited treatment options.
- Current chemotherapy for OS suffers from poor drug bioavailability, permeability, and significant side effects.
- Developing targeted drug delivery systems is crucial for improving OS treatment efficacy.
Purpose of the Study:
- To develop a near-infrared light (NIR)-driven and glutathione (GSH)-responsive nanomotor for enhanced osteosarcoma treatment.
- To improve drug penetration and localized drug release within the tumor microenvironment.
- To investigate the synergistic therapeutic effects of doxorubicin and platinum nanoparticles in an OS model.
Main Methods:
- Synthesized a poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor.
- Utilized NIR light for photothermal activation and propulsion of the nanomotor.
- Incorporated disulfide bonds for GSH responsiveness and platinum nanoparticles for ROS generation.
- Evaluated nanomotor speed, drug release kinetics, cytotoxicity, ROS production, and in vivo tumor growth inhibition.
Main Results:
- The PSPDP nanomotor demonstrated enhanced movement speed (2.10-fold increase) under NIR exposure due to photothermal properties.
- Doxorubicin (DOX) release efficiency increased with GSH concentration, indicating favorable GSH responsiveness.
- Platinum nanoparticles (Pt-NPs) generated reactive oxygen species (ROS), synergistically enhancing DOX's therapeutic effect, leading to a 5.53-fold increase in OS cell growth inhibition.
- Significant inhibition of osteosarcoma growth was observed in a nude mice model with minimal cytotoxicity.
Conclusions:
- The NIR-driven, GSH-responsive PSPDP nanomotor offers a promising strategy for localized and targeted osteosarcoma treatment.
- Enhanced drug delivery and controlled release improve therapeutic efficacy while minimizing systemic toxicity.
- The combination of photothermal propulsion, ROS generation, and targeted drug delivery represents a significant advancement in OS therapy.
