The invention discloses an active targeting type amphiphilic polypeptide composite nano-
micelle prodrug as well as preparation and application thereof, and belongs to the technical field of biological medicines. The composite nano-
micelle prodrug is obtained by co-assembling a first polypeptide with negative charges and a second polypeptide with positive charges through
electrostatic interaction and hydrophilic and hydrophobic effects; the first polypeptide is Lys-AAm-Gly-Arg-Gly-Asp-Ser, wherein AA is
aspartic acid or
glutamic acid, and m is 1, 2, 3 or 4; the second polypeptide is Cys-BBn, wherein BB is
lysine,
arginine or
histidine, and n is 1, 2, 3 or 4; amino at a N end of the first polypeptide is connected with a hydrophobic
alkyl chain, and amino at a
lysine side chain of the first polypeptide is connected with a fluorescent molecule;
cysteine in the second polypeptide is covalently linked with an anti-tumor
drug through sulfydryl. The nano-composite
micelle can be actively targeted to
tumor cells, and is disassembled after responding to a tumor slightly acidic environment to form a small-size micelle with a size of 20-30 nm, so that deep delivery of the polypeptide anti-tumor
prodrug at a tumor part is facilitated.