Folic acid grafted and tertiary amino based pH-responsive pentablock polymeric micelles for targeting anticancer drug delivery

- Folic acid grafted pH-responsive pentablock copolymers were successfully synthesized and characterized.
- The pH-responsive pentablock polymeric DOX-loaded micelles were prepared and measured.
- The self-assembled micelles could target tumor cells rapidly, control drug release.
- The DOX-loaded micelles could provide equivalent toxic effective of free DOX and deliveried into tumor cells effectively

Increasing target to tumor sites and reducing accumulation at normal tissue sites of anticancer drugs are essential to improve the cancer chemotherapy efficiency. In this study, we have developed a novel pentablock polymeric poly(ethylene glycol)-b-(poly(2-(diethylamino) ethyl methacrylate)-b-poly (hydroxyethyl methacrylate)-g-folic acid)2 [PEG-b-(PDEAEMA-b-PHEMA-g-FA)2] micelles as anticancer drug nanocarrier. The carriers could target tumor cells rapidly, and response to the tumor sites pH to control drug release. The critical micelle concentration (CMC) of the intermediates copolymers was 4.37-7.08 mg/L, which indicated that the self-assembled micelles had comparatively good internal circulation stability. The drug loaded micelles were prepared using dialysis method, resulting in an average particle size of below 120 nm, and the drug loading content and entrapment efficiency were 21% and 48% respectively. The pH-responsiveness and in vitro drug release of the micelles were studied, and the results showed a higher doxorubicin (DOX) cumulative amount at pH 5.0 (~ 90%) compared to pH 7.4 (~ 20%) owing to the protonation of the tertiary amino groups. In vitro cytotoxicity and endocytosis experiments showed that the tumor-suppressing effect of drug-loaded micelles was close to those of free DOX. The loaded DOX could be delivered into the cancer cells in a short time, and about 80% of the tumor cells were killed after 48 h incubation. The results indicate that the pentablock polymeric micelles have the potential to be applied for targeting anticancer drug delivery and control release.

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