Antineoplastic Drug‐Free Anticancer Strategy Enabled by Host‐Defense‐Peptides‐Mimicking Synthetic Polypeptides
An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechani...
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| Published in | Advanced materials (Weinheim) Vol. 32; no. 36; pp. e2001108 - n/a |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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01.09.2020
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| Abstract | An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane‐lytic mechanism. Moreover, a pH‐sensitive zwitterionic derivative of ACPP (DA‐ACPP) is prepared for in vivo application. DA‐ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA‐ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16‐F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs‐mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug‐free synthetic polymers for cancer therapy.
An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is proposed. The synthetic anticancer polypeptides (ACPP) exhibit broad‐spectrum anticancer activity through an HDPs‐like membrane‐lytic mechanism. Modification of ACPP with 2,3‐dimethylmaleic anhydride (DA) generates a pH‐sensitive zwitterionic derivative, DA‐ACPP, with improved biocompatibility, which can selectively lyse tumors in vivo after being activated in acidic tumor microenvironment. |
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| AbstractList | An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane‐lytic mechanism. Moreover, a pH‐sensitive zwitterionic derivative of ACPP (DA‐ACPP) is prepared for in vivo application. DA‐ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA‐ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16‐F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs‐mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug‐free synthetic polymers for cancer therapy.
An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is proposed. The synthetic anticancer polypeptides (ACPP) exhibit broad‐spectrum anticancer activity through an HDPs‐like membrane‐lytic mechanism. Modification of ACPP with 2,3‐dimethylmaleic anhydride (DA) generates a pH‐sensitive zwitterionic derivative, DA‐ACPP, with improved biocompatibility, which can selectively lyse tumors in vivo after being activated in acidic tumor microenvironment. Abstract An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane‐lytic mechanism. Moreover, a pH‐sensitive zwitterionic derivative of ACPP (DA‐ACPP) is prepared for in vivo application. DA‐ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA‐ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16‐F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs‐mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug‐free synthetic polymers for cancer therapy. An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits a broad spectrum of anticancer activity in 12 cancer cell lines, including drug‐resistant and highly metastatic tumor cells. Detailed mechanistic studies reveal that the cationic anticancer polypeptide (ACPP) can directly induce rapid necrosis of cancer cells within minutes through a membrane‐lytic mechanism. Moreover, a pH‐sensitive zwitterionic derivative of ACPP (DA‐ACPP) is prepared for in vivo application. DA‐ACPP shows negligible hemolysis under neutral physiological conditions, and can be converted back to ACPP in slightly acidic tumor environments, resulting in selective killing of cancer cells. Consequently, DA‐ACPP shows an effective inhibition of tumor growth in both 4T1 orthotopic breast tumor models and B16‐F10 melanoma pulmonary metastatic models. Overall, these findings demonstrate that synthetic HDPs‐mimicking polypeptides represent safe and effective antineoplastic agents, which sheds new light on the development of drug‐free synthetic polymers for cancer therapy. |
| Author | Chen, Xuesi Zhang, Peng An, Lin Zhang, Yu Shen, Wei Wan, Pengqi Xiao, Chunsheng |
| Author_xml | – sequence: 1 givenname: Wei surname: Shen fullname: Shen, Wei organization: University of Chinese Academy of Sciences – sequence: 2 givenname: Yu surname: Zhang fullname: Zhang, Yu organization: Chinese Academy of Sciences – sequence: 3 givenname: Pengqi surname: Wan fullname: Wan, Pengqi organization: Northeast Normal University – sequence: 4 givenname: Lin surname: An fullname: An, Lin organization: Jilin University – sequence: 5 givenname: Peng surname: Zhang fullname: Zhang, Peng organization: Jilin Biomedical Polymers Engineering Laboratory – sequence: 6 givenname: Chunsheng surname: Xiao fullname: Xiao, Chunsheng email: xiaocs@ciac.ac.cn organization: Jilin Biomedical Polymers Engineering Laboratory – sequence: 7 givenname: Xuesi orcidid: 0000-0003-3542-9256 surname: Chen fullname: Chen, Xuesi email: xschen@ciac.ac.cn organization: Jilin Biomedical Polymers Engineering Laboratory |
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| Snippet | An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide exhibits... Abstract An antineoplastic drug‐free anticancer strategy enabled by host defense peptides (HDPs)‐mimicking synthetic polypeptides is reported. The polypeptide... |
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| SubjectTerms | anticancer Anticancer properties Cancer Materials science membrane‐lytic strategies Metastasis Necrosis Peptides pH‐sensitivity polymer therapeutics Polypeptides Tumors |
| Title | Antineoplastic Drug‐Free Anticancer Strategy Enabled by Host‐Defense‐Peptides‐Mimicking Synthetic Polypeptides |
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