Study on Gene Delivery System Mediated by T Cell Membrane Modification for Low-Temperature Photothermal Therapy of Glioma
GAO Xiaohan1, SUN Zhihong2, LIU Jie2, ZHAO Qi2, SUN Chengming1,2*
Gliomas are the most common malignant tumors of the central nervous system and face challenges such as resistance from heat shock proteins and obstacles posed by the blood-brain barrier during lowtemperature photothermal therapy. In this study, a novel gene delivery system, aT@FVNPs, is synthesized by modifying T cell membranes with photothermal agents and HSP90-siRNA on the surface of carriers. This system aims to achieve effective low-temperature photothermal therapy for gliomas. The basic properties of the carriers were determined using a nanoparticle size analyzer, UV-visible spectrophotometer, and fluorescence spectrometer. The performance of aT@FVNPs in penetrating endothelial cells and the ability to knock down HSP90 and kill tumor cells in vitro were assessed using mouse endothelial cells (Bend.3) and glioma cells (GL261). The results showed that aT@FVNPs more readily crossed the endothelial cell barrier and induced stronger glioma cell killing under low-temperature photothermal conditions due to HSP90 knockdown. Additionally, using a mouse orthotopic glioma model, the in vivo targeting potential of aT@FVNPs was further evaluated, demonstrating a stronger accumulation at the glioma site compared to the FVNPs group. With laser irradiation, aT@FVNPs group showed more obvious pathological necrosis and induced cell apoptosis. In summary, aT@FVNPs can cross the blood-brain barrier and target glioma sites, effectively killing tumor cells under low-temperature photothermal conditions by inhibiting heat shock protein expression.
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