The invention belongs to the technical field of medicines, and particularly relates to enhanced penetration type double-response nanoparticles for co-delivery of
chemotherapeutic drugs and
gene drugs as well as a preparation method and application thereof. According to the invention,
albumin is used as a carrier of
gemcitabine, an ROS responsive charge reversible cationic
polymer is used as a delivery carrier of siRNA, and
gemcitabine drug-loaded
albumin and siRNA
drug-loaded B-PDEA nanoparticles are coupled through MMP-2 responsive polypeptide to form the
drug-loaded nanoparticles. After reaching a tumor area through the active targeting effect of
albumin, the nanoparticles can be
cut by MMP-2 in a microenvironment and release drug-loaded albumin, so that the size of a
delivery system is reduced, and further tumor
deep penetration and enhanced
gemcitabine uptake are realized; meanwhile, after
intracellular high-level ROS is recognized, the loaded siRNA can be selectively released and inhibit CD39 expression, tumor
metabolism is adjusted, an
immune microenvironment is remodeled and an anti-tumor immune response is activated to further realize
chemotherapy sensitization while precise
chemotherapy is performed, and the therapeutic
efficacy on
pancreatic cancer is expected to be enhanced.