The use of cationic MPEG-PCL-g-PEI micelles for co-delivery of Msurvivin T34A gene and doxorubicin

Abstract

In our previous study, a series of triblock copolymers based on MPEG-PCL-g-PEI were successfully synthesized, and the physicochemical properties of their self-assembled micelles were also investigated. Here, a further evaluation of these micelles was carried out, including in vitro drug release behavior, body distribution as well as blood compatibility. The developed MPEG-PCL-g-PEI micelles was labeled with (99)Tc for tracing the body distribution of micelles after i.v. injection, and the results showed that the MPEG-PCL-g-PEI micelles mainly concentrated in the tumor tissue. Meanwhile, the anti-tumor activity on both B16F10 subcutaneous tumor model and lung metastasis model was tested and the results indicated that DOX-loaded micelles could significantly inhibit tumor growth as compared with free doxorubicin, which was accompanied by significantly increased apoptosis of tumor cells. By introduction of gene Msurvivin T34A in combination with chemotherapies in the treatment of lung metastasis tumor, it could greatly reduce systemic toxicity as well as improved the anti-tumor efficiency. These results demonstrated that it is possible to use cationic MPEG-PCL-g-PEI micelles for effectively co-delivering functional gene and chemotherapeutic agent, and thus improving anti-tumor effect and systemic toxicity.

Keywords: Cancer therapy; Cationic micelles; Co-delivery vector; Triblock copolymer.