The invention discloses a double-targeting polypeptide-
antibody-
drug conjugate, and a prepared method and antineoplastic application thereof. The double-targeting polypeptide-
antibody-
drug conjugate structurally includes four components of (A), tumor specificity targeting polypeptide; (B), an
antineoplastic drug; (C), a mitochondria target functional group; and (D),
hydrazone bonds used for connecting the polypeptide and the
antineoplastic drug. The tumor specificity targeting polypeptide is connected with the
antineoplastic drug by a connecting arm comprising the
hydrazone bonds; the antineoplastic
drug is connected with the mitochondria target functional group by chemical bonds; and the tumor specificity targeting polypeptide is suitable for targeting the conjugate to a tumour
cell and marker
protein LAPTM4B carried on the surface of the tumour
cell is used as a specificity target. A molecular target is combined with an
organelle target, selective uptake of the drug in the tumour
cell can be increased, an acting site of a DOX drug can be transferred form
cell nucleus to mitochondria, and therefore the condition that the tumour cell is killed by
drug resistance is avoided.