Reduction-sensitive mixed micelles based on mPEG-SS-PzLL /TPGS to enhance anticancer efficiency of doxorubicin

Currently, the drawbacks of the chemotherapy drugs are still demonstrated poor water solubility, systemic toxicity and even multidrug resistance (MDR) in clinical applications. To address these problems, an amphiphilic block polymer self-assembled reduction sensitive micelle, mPEG-SS-PzLL/TPGS/DOX, was synthesized for efficient anticancer therapy. The polymer had a biodegradable backbone and disulfide bond can be cleaved by reduced glutathione (GHS) in tumor cells, which led to fast release of the DOX. TPGS was designed for an increaseing drug accumulation and a reduction in drug efflux.

Highlights

• A block polymer with reduction responsiveness was synthesized through a simple process.

• Self-assembled mixed micelles have the advantages of high encapsulation efficiency and high stability.

• TPGS inhibits multidrug resistance and increases the uptake of drugs by 4T1cells.

• Reduction-responsive micelles show a intense therapeutic effect on Balb/c mice loaded with 4 T1 cells.

In follow-up research, we found that mPEG-SS-PzLL/TPGS/DOX micelles achieved a high encapsulation efficiency of 96.1%. Photomicrographs gotten by TEM showed homogeneous and spherical-shaped particles with the particl size of 83.7 ± 3.2 nm. The in vitro release in high reducing conditions reached 96% within 48 h. Furthermore, the mPEG-SS-PzLL/TPGS/DOX micelles caused stronger cytotoxicity to 4 T1 cells and promising therapeutic efficacy for BALB/c mice bearing 4 T1 tumors. Therefore, an excellent drug delivery system was created by combing restore sensitivity with multidrug resistance strategy while maximize drug accumulation in tumor cells. Alternatively, this study offers a bright perspective for cancer therapy with chemotherapeutics.

See the article

Guoguang Chen, Qiqi Zheng, Jie Dai, Jia Liu, Jun Yin, Xiaoqing Xu, Aiping Chen, Lili Ren,
Reduction-sensitive mixed micelles based on mPEG-SS-PzLL /TPGS to enhance anticancer efficiency of doxorubicin,
Reactive and Functional Polymers, Volume 174, 2022, 105242, ISSN 1381-5148,
https://doi.org/10.1016/j.reactfunctpolym.2022.105242.