A Biomimetic Nanoplatform for Near-Infrared-Assisted Heat-Mediated Synergistic Therapy for Glioblastoma

Cell membrane (CM) camouflage has emerged as a powerful biomimetic strategy for enhancing the precision of targeted drug delivery, offering an effective solution to the major limitations of phototheranostic nanomaterials, which often suffer from reduced therapeutic efficacy and imaging performance due to tumor heterogeneity and microenvironmental delivery barriers. Here, we report a biomimetic phototheranostic nanoplatform engineered for the synergistic treatment of glioblastoma multiforme (GBM) via near-infrared (NIR)-assisted, heat-enhanced chemotherapy. Magnetic nanoparticles (M) with improved stability and biocompatibility were synthesized to enable efficient magnetic hyperthermia. These nanoparticles were further functionalized with cancer CM and temozolomide (TMZ)-conjugated, cell-penetrating peptide-based copolymers (P), providing homotypic targeting capability and enhanced intratumoral accumulation. This multifunctional coating significantly improved selectivity toward GBM cells and enabled combined photothermal and chemotherapeutic activity. Cellular studies under both illuminated and dark conditions revealed pronounced synergistic cytotoxicity arising from the integration of NIR-mediated magnetic hyperthermia with TMZ delivery. Compared to nonpolymer-functionalized controls, the proposed system more effectively overcame tumor heterogeneity and microenvironmental barriers, yielding superior therapeutic performance. These findings highlight the potential of this biomimetic platform for targeted and multimodal GBM theranostics. Overall, this work introduces a versatile biomimetic nanocamouflage strategy that leverages natural cellular functionalities and nanotechnology to advance targeted GBM therapy, providing a promising avenue for more precise and effective treatment of highly malignant brain tumors.