Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents

Author:

Pan Miao123,Lu Chao4ORCID,Zhang Wancong123,Huang Huan5,Shi Xingyu5,Tang Shijie123,Liu Daojun5

Affiliation:

1. Plastic Surgery Institute of Shantou University Medical College, Shantou 515041, China

2. Department of Plastic Surgery and Burn Center, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China

3. Shantou Plastic Surgery Clinical Research Center, Shantou 515041, China

4. College of Pharmacy, Jinan University, Guangzhou 511436, China

5. Department of Pharmacy, Shantou University Medical College, Shantou 515041, China

Abstract

Anticancer peptides and polymers represent an emerging field of tumor treatment and can physically interact with tumor cells to address the problem of multidrug resistance. In the present study, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides were prepared and evaluated as macromolecular anticancer agents. Amphiphilic PLO-b-PLF self-assembles into nanosized polymeric micelles in aqueous solution. Cationic PLO-b-PLF micelles interact steadily with the negatively charged surfaces of cancer cells via electrostatic interactions and kill the cancer cells via membrane lysis. To alleviate the cytotoxicity of PLO-b-PLF, 1,2-dicarboxylic-cyclohexene anhydride (DCA) was anchored to the side chains of PLO via an acid-labile β-amide bond to fabricate PLO(DCA)-b-PLF. Anionic PLO(DCA)-b-PLF showed negligible hemolysis and cytotoxicity under neutral physiological conditions but recovered cytotoxicity (anticancer activity) upon charge reversal in the weakly acidic microenvironment of the tumor. PLO-based polypeptides might have potential applications in the emerging field of drug-free tumor treatment.

Funder

2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant

Guangdong University Innovation Team Project

Guangdong Science and Technology Special Fund

Publisher

MDPI AG

Subject

Pharmaceutical Science

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