Genetically light-enhanced immunotherapy mediated by a fluorinated reduction-sensitive delivery system.

ABSTRACT

The lack of safe and efficient therapeutic agent delivery platforms restricts combined therapy's effect, and combined cancer therapy's multi-component delivery effect needs improvement. The novel gene delivery system SS-HPT-F/pMIP-3ß-KR was proposed to construct fluorine-containing degradable cationic polymers SS-HPT-F by a mild and simple amino-epoxy ring-opening reaction. By modifying the fluorinated alkyl chain, the delivery efficiency of the plasmid was greatly improved, and the cytoplasmic transport of biomolecules was completed. At the same time, a combination plasmid (MIP-3ß-KillerRed) was innovatively designed for the independent expression of immune and photodynamic proteins. Which was efficiently transported to the tumor site by SS-HPT-F. The MIP-3ß is expressed as an immune chemokine realize the immune mobilization behavior. The photosensitive protein KillerRed expressed in the tumor killed cancer cells under irradiation and released the exocrine immune factor MIP-3ß. The immunogenic cell death (ICD) produced by photodynamic therapy (PDT) also induced the immune response of the organism. The synergistic effect of PDT and MIP-3ß mobilized the immune properties of the organism, providing light-enhanced immune combination therapy against malignant tumors. Therefore, in subcutaneous tumor-bearing and metastatic animal models, the carrier tumor growth and mobilize organism produce an immune response without systemic toxicity. This work reports the first efficient gene delivery system that achieves light-enhanced immunotherapy.