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.本發明提供一種循序崩解之帶殼多胜肽奈米載體及其製備方法,該載體包含可自我聚合的長鏈及短鏈多胜肽共聚物,其中長、短鏈多胜肽共聚物各包含長、短鏈親水性聚合物及一多胜肽,該多胜肽依序包含酸性胺基酸鏈段、酸敏感性胺基酸鏈段、及疏水性胺基酸鏈段,該長鏈親水性聚合物與該多胜肽以一酸不穩定鍵結連接,該短鏈親水性聚合物末端連接一主動標靶分子,且一酸可溶性礦物於該酸性胺基酸鏈段分次沉積形成一酸可溶性礦化保護殼層。本發明亦提供使用該帶殼多胜肽奈米載體的醫藥組合物,可包覆疏水性藥物以抑制腫瘤及其轉移。
