A Novel pH-Tunable Secondary Conformation Containing Mixed Micellar System in Anticancer Treatment

• Main Authors: Fu-Ying Shih, Wen-Ping Jiang, Xiaojie Lin, Sheng-Chu Kuo, Guan-Jhong Huang, Yu-Chi Hou, Chih-Shiang Chang, Yang Liu, Yi-Ting Chiang
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Cancers
• Subjects: secondary structure; mixed micelle; ph responsive; drug delivery system
• Online Access: https://www.mdpi.com/2072-6694/12/2/503

In this study, for the first time, we precisely assembled the poly-γ-benzyl-l-glutamate and an amphiphilic copolymer d-α-tocopherol polyethylene glycol succinate into a mixed micellar system for the embedment of the anticancer drug doxorubicin. Importantly, the intracellular drug-releasing behaviors could be controlled by changing the secondary structures of poly-γ-benzyl-l-glutamate via the precise regulation of the buffer’s pH value. Under neutral conditions, the micellar architectures were stabilized by both α-helix secondary structures and the microcrystalline structures. Under acidic conditions (pH 4.0), the interior structures transformed into a coil state with a disordered alignment, inducing the release of the loaded drug. A remarkable cytotoxicity of the Dox-loaded mixed micelles was exhibited toward human lung cancer cells in vitro. The internalizing capability into the cancer cells, as well as the intracellular drug-releasing behaviors, were also identified and observed. The secondary structures containing Dox-loaded mixed micelles had an outstanding antitumor efficacy in human lung cancer A549 cells-bearing nude mice, while little toxicities occurred or interfered with the hepatic or renal functions after the treatments. Thus, these pH-tunable α-helix-containing mixed micelles are innovative and promising for controlled intracellular anticancer drug delivery.