Self-assembled intelligent nano-delivery system with targeting for cascade anti-tumor therapy

Single antitumor therapy is difficult to completely cure the tumor, and there is a risk of metastasis and recurrence. Based on this, we proposed a cascade antitumor therapy. Firstly, self-assembly PdCl₂ was guided by lanreotide to form Pd nano-cubes by simulating biomineralization for antitumor photothermal therapy. Subsequently, siRNA was loaded on it for anti-tumor gene therapy, which can realize responsive drug release based on NIR stimulation and enhance the biosafety of gene therapy. Subsequently, the tumor cell membrane was wrapped to form an intelligent nano-delivery system PdCS@M, which can be used to enhance the active targeting efficiency of the nano-delivery system against the tumor and enhance the anti-tumor effect. Finally, photothermal/gene combination induced tumor cell apoptosis to trigger immunogenic cells death, completely inhibit tumor growth. Long-term immune memory was existed to inhibit tumor recurrence and metastasis. The development of the intelligent nano-delivery system, which enhanced the biosafety of gene therapy, in combination with photothermal therapy, can trigger immunogenic death and achieve anti-tumor cascade therapy. In vitro and in vivo experiments showed that the tumor inhibition rate of cascade therapy was much higher than that of other treatment groups, and it had great clinical transformation potential in the field of nanomedicine.

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