Fabrication of Polymer Micelles with Zwitterionic Shell and Biodegradable Core for Reductively Responsive Release of Doxorubicin

• Published in: Polymers Vol. 11; no. 6; p. 1019
• Main Authors: Jiang, Junting, Li, Junbo, Zhou, Biyu, Niu, Chaohuang, Wang, Wendi, Wu, Wenlan, Liang, Ju
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.06.2019; MDPI
• Subjects: Addition polymerization; anticancer drugs; Biodegradability; Biodegradation; Block copolymers; Chain transfer; disulfide-linker; Doxorubicin; Drug delivery systems; Drugs; Hemodialysis; Micelles; Molecular chains; Nanoparticles; Nitrogen; Physiology; poly-ε-caprolactone; polycarboxybetaine; Polyethylene glycol; Polymers; Proteins; Reagents; release; Self-assembly; Solvents; Spectrum analysis; Stability; triblock copolymer; Zwitterions; Beijing China; China; polycarboxybetaine; poly-ε-caprolactone; disulfide-linker; anticancer drugs; release; triblock copolymer
• ISSN: 2073-4360; 2073-4360
• DOI: 10.3390/polym11061019

To achieve a high stability in physiological environment and rapid intracellular drug release, a biodegradable zwitterionic triblock copolymer with a disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCBMA-SS-PCL-SS-PCBMA) was prepared for micellar carrier to delivery doxorubicin (DOX) into tumor cells. PCBMA-SS-PCL-SS-PCBMA was obtained by following steps: i) introducing disulfide bonds through end-group modification of PCL diol with cystamine dihydrochloride; ii) preparing PCL-RAFT macromolecular chain transfer agent by EDC/NHS chemistry; iii) RAFT polymerization of zwitterionic monomer. Self-assembling from PCBMA-SS-PCL-SS-PCBMA, polymeric micelles had many advantages, such as ultra-low protein absorption in serum and obvious reduction-responsiveness in the presence of DTT. Furthermore, DOX-loaded micelles exhibited high stability upon centrifugation and lyophilization, a fast intracellular drug release and enhanced drug efficacy due to GSH-triggered PCBMA shell shedding and micellar reassembling. Thus, the polymeric micelles integrated several functions and properties could be prospectively utilized as valuable nanocarriers in cancer chemotherapeutics.