Microwave‐Responsive AIE Nanocomposite Induces Immunogenic Senescence for Imaging‐Guided Therapy and Bone Repair in Osteosarcoma
Year: 2026
Type: article
Abstract: Osteosarcoma remains challenging due to incomplete tumor resection, local recurrence, and limited immunostimulatory efficacy of current microwave (MW)-based therapies. Here, we develop a multifunctional theranostic nanoplatform, GPC3@TTBC, by conjugating an osteosarcoma-targeting anti-GPC3 peptide onto aggregation-induced emission (AIE) nanoparticles. GPC3@TTBC enables selective tumor accumulation and high-contrast near-infrared fluorescence imaging, allowing precise tumor margin delineation and superior tumor-to-background resolution compared with clinically used dyes, including effective visualization in patient-derived xenograft models. Upon MW irradiation, lysosome-localized GPC3@TTBC generates robust nonthermal reactive oxygen species (ROS) through enhanced charge separation and electron transfer, resulting in substantial tumor cell apoptosis while simultaneously inducing a prominent immunogenic senescence-associated phenotype and senescence-associated secretory phenotype (SASP) response. Importantly, MW + GPC3@TTBC suppressed tumor cell migration and invasion in vitro and reduced pulmonary metastatic lesions in vivo. Meanwhile, the SASP promoted dendritic cell maturation and cytotoxic T lymphocyte activation, thereby enhancing antitumor immune responses and remodeling the tumor immune microenvironment. Beyond tumor eradication, GPC3@TTBC facilitates osteogenic microenvironment reconstruction and bone regeneration after tumor clearance, while exhibiting favorable biosafety. Collectively, GPC3@TTBC integrates targeted fluorescence-guided imaging, MW-enhanced ROS generation, immunogenic senescence induction, and bone regeneration, providing a comprehensive theranostic strategy for precise osteosarcoma treatment.
Source: Advanced Healthcare Materials
DOI: 10.1002/adhm.71934
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W7225232540