Osteosarcoma (OS) presents formidable challenges due to its aggressive progression and resistance to conventional therapies. Recent advancements in multimodal strategies, such as combining gene therapy with mild-temperature photothermal therapy (mPTT), referred to as GT-mPTT, have shown promise in enhancing therapeutic efficacy while minimizing side effects. However, current systems face limitations in therapeutic response, efficiency, and biosafety. Herein, we report a reactive oxygen species (ROS)-responsive polymeric amphiphile for imaging-guided combinational GT-mPTT therapy, achieving a high-efficiency antitumor performance against OS. This polymer incorporates guanidine-functionalized units for effective gene condensation and near-infrared II (NIR-II) active dyes for efficient photothermal conversion. The system exhibits charge reversal under elevated intratumoral ROS levels, promoting gene release, and achieves controlled mild hyperthermia under NIR-II irradiation, enhancing cellular uptake and enabling effective mPTT. The GT-mPTT combination therapy, guided by dual NIR-II fluorescence and photothermal imaging, demonstrated significant therapeutic outcomes in vitro and in vivo. These include pronounced tumor cell apoptosis, substantial tumor size reduction, and mitigation of osteolysis in OS-bearing mouse models, all while maintaining excellent biosafety and negligible systemic toxicity. This work shows the potential of responsive polymeric platforms with integrated multimodal therapeutic and imaging capabilities as a robust foundation for advancing precision therapies against OS.
Tang et al. (Tue,) studied this question.
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