Cell Membrane-Encapsulated Biomimetic Nanomedicines Carrying siRNA for Glioblastoma Treatment via Gene Silencing Synergistic Phototherapy

The synergy between phototherapy and gene therapy, which relies on photothermal promotion of siRNA release to achieve regulation of RNA interference genes, has resulted in excellent synergy and high efficacy of combined phototherapy-gene therapy, which has shown great potential in tumor therapy. Here, we synthesized gold nanomaterials (Au NRs) with near-infrared absorption and piggybacked Bcl-2 siRNAs (Bcl-2@Au NPs) on their surfaces using a silver (Ag) template method. In addition, the tumor cell membrane (CM) was modified on the surface to consider the effect of the blood-brain barrier in the brain, which resulted in a higher targeting ability of Bcl-2@Au NPs -CM to the glioblastoma region. Under the irradiation of NIR light, the temperature of Bcl-2@Au NPs-CM accumulated at the tumor site increased to induce apoptosis in tumor cells. The main function of Bcl-2 as an apoptosis inhibitory protein is to protect cells from apoptosis by inhibiting the activity of apoptotic factors, which would hinder the effect of phototherapy on tumor cells. However, Bcl-2 siRNA released from Bcl-2@Au-CM NPs in tumor cells inhibits the overexpression of Bcl-2 in the cytoplasm, which would exacerbate the apoptotic effect of phototherapy. Therefore, the anti-tumor efficacy of the administration therapy of Bcl-2@Au-CM NPs was significantly improved due to the efficient synergistic delivery ability of phototherapy-gene therapy. Phototherapy and gene therapy are synergistic and mutually reinforcing, and have excellent prospects for clinical application in the field of tumor therapy.