Alkaline Phosphatase-Activated NIR-II AIEgens Nanosystem for Surgical and Postoperative Closed-Loop Therapy of...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Advanced osteosarcoma presents challenges in complete resection due to tumor invasion.
• The immunosuppressive tumor microenvironment limits the efficacy of current immunotherapies.
• Residual or metastatic lesions are primary drivers of osteosarcoma recurrence.

Purpose of the Study:

• To develop an Alkaline Phosphatase (ALP)-responsive theranostic nanoplatform for imaging-guided resection and multimodal therapy in osteosarcoma.
• To integrate Aggregation-Induced Emission luminogens (AIEgens) and an HSP90 inhibitor for enhanced therapeutic effects.
• To address tumor hypoxia and reverse lactate-driven immunosuppression.

Main Methods:

• Development of a Selenium-doped AIEgen (STEA) for Near-Infrared IIb (NIR-IIb) imaging and phototherapy.
• Integration of Ganetespib (HSP90 inhibitor) within an ALP-responsive nanomicelle structure.
• NIR irradiation to induce pyroptosis and immunogenic cell death, combined with Ganetespib to suppress glycolysis.

Main Results:

• The nanoplatform (SGPF) achieved effective NIR-IIb imaging for precise resection guidance.
• ALP-triggered release of STEA and Ganetespib, coupled with perfluorohexane vaporization, effectively relieved tumor hypoxia.
• Combined phototherapy and Ganetespib treatment induced pyroptosis and immunogenic cell death, suppressed glycolysis, and reversed immunosuppression.

Conclusions:

• The developed theranostic nanoplatform demonstrates synergistic effects in enhancing T-cell infiltration and ablating residual/metastatic osteosarcoma lesions.
• This dual-action strategy offers a promising therapeutic approach for unresectable osteosarcoma.
• The study highlights the potential of nanomedicine in overcoming challenges in advanced cancer treatment.