The invention relates to a bionic intelligent microneedle tumor vaccine as well as a preparation method and application thereof. According to the vaccine, coaxial electrostatic spraying is utilized to construct a
drug-loaded
microsphere with a core-shell structure, the
drug-loaded
microsphere is coated with
cancer cell-derived
membrane protein, and then the
drug-loaded
microsphere is fixed at the needle point part of a soluble microneedle in a centrifugal manner, so that local
drug delivery of crossing a
cuticle layer and accurately delivering the drug-loaded microsphere to a corium layer is realized. The microsphere can load demethylated drugs DAC and TAM at the same time, and realizes responsive
controlled release in a
tumor microenvironment. A plurality of tumor-associated antigens and
apoptosis-associated injury-associated molecular patterns carried by the
cancer cell membrane protein can promote the maturation of dendritic cells and activate the specific
T cell mediated anti-tumor immune response. In conclusion, the microneedle vaccine
system integrates multiple functions of precise delivery, controllable release,
chemical kinetics treatment, epigenetic regulation,
immune activation and the like, the anti-tumor
immunotherapy effect can be effectively enhanced, and a new strategy is provided for tumor
immunotherapy.