Abstract
Provided is a sequentially decomposable polypeptide-based nanocarrier with shell and preparation thereof. The nanocarrier comprises and self-assembles from a polypeptide-based long chain copolymer and a polypeptide-based short chain copolymer, wherein the polypeptide-based long chain copolymer and the polypeptide-based short chain copolymer comprise a long-chain hydrophilic polymer and a short-chain hydrophilic polymer respectively and a polypeptide. The polypeptide sequentially comprises a segment of acidic amino acids, a segment of acid-responsive amino acids, and a segment of hydrophobic amino acids; the long-chain hydrophilic polymer is conjugated with the polypeptide via an acid labile linkage; the short-chain hydrophilic polymer has an end conjugated with an active targeting molecule; and the nanocarrier has an acid-hydrolyzed mineralized protective layer formed at the segment of acidic amino acids by sequential deposition of acid-soluble mineral. Also provided is a pharmaceutical composition, comprising the nanocarrier encapsulating a hydrophobic drug for inhibition of tumor growth and metastasis.