Work

Alkaline Phosphatase‐Activated NIR‐II AIEgens Nanosystem for Surgical and Postoperative Closed‐Loop Therapy of Advanced Osteosarcoma

Year: 2026

Type: article

Abstract: In advanced osteosarcoma, tumor invasion often prevents complete resection, and immunotherapy is limited by the tumor's immunosuppressive nature, making residual lesions a key source of recurrence. To address this, we developed an ALP-responsive theranostic nanoplatform (SGPF) integrating an AIEgens (STEA) and HSP90 inhibitor (Ganetespib) for imaging-guided resection and multimodal therapy. Selenium-doped STEA enables NIR-IIb imaging and enhanced phototherapy via narrowed HOMO-LUMO gaps and nonradiative decay optimization. At tumor sites, ALP-triggered nanomicelle cleavage releases STEA and Ganetespib while vaporizing perfluorohexane to relieve hypoxia. NIR irradiation induces pyroptosis via caspase-3/GSDME activation and immunogenic cell death, while Ganetespib suppresses glycolysis (HK2/PKM2 downregulation) to reverse lactate-driven immunosuppression. This dual-action strategy synergistically enhances T-cell infiltration and ablates residual/metastatic lesions, offering a transformative approach for unresectable Osteosarcoma.

Source: Advanced Science

DOI: 10.1002/advs.202516035