Abstract
Provided is a sequentially decomposable polypeptide-based nanocarrier with protective shell for delivery of hydrophobic drugs and preparation thereof. The nanocarrier includes a polypeptide-based long chain copolymer and a polypeptide-based short chain copolymer both assembling into an outer layer of hydrophilic polymer and a polypeptide core, wherein the polypeptide-based long chain copolymer includes a long-chain hydrophilic polymer and a first polypeptide chain; the polypeptide-based short chain copolymer includes a short-chain hydrophilic polymer and a second polypeptide chain; the first and the second polypeptide chains each sequentially includes an acidic amino acid segment, an acid-responsive amino acid segment, and a hydrophobic amino acid segment; the long-chain hydrophilic polymer is conjugated with the first polypeptide chain via an acid-labile linkage; an end of the short-chain hydrophilic polymer is conjugated with an active targeting molecule; and the polypeptide core includes a protective shell of an acid-soluble mineral on the acidic amino acid segment.