Vitamin E-tocopheryl polyethylene glycol succinate decorated drug delivery system with synergistic antitumor effects to reverse drug resistance and immunosuppression

To overcome cancer drug resistance and to reverse tumor immunosuppression, a vitamin E-tocopheryl polyethylene glycol succinate (TPGS) decorated polymer-based drug delivery system was developed. The effects of the drug delivery system on diverse proteins involved in cell apoptosis, cancer invasion, metastasis and immunosuppression were investigated to provides a more comprehensive understanding of TPGS modified drug delivery systems. Curcumin (CUR), a hydrophobic drug, was loaded in star poly(DL-lactide) with a cholic acid core, and then decorated with TPGS shell to obtain [email protected]/star poly(DL-lactide) nanoparticles ([email protected]).

Highlights

A TPGS decorated drug delivery system was constructed to overcome cancer drug resistance.

The delivery system can reverse cancer drug resistance through down-regulating P-gp expression.

The system efficiently downregulates cancer-promoting proteins to inhibit cancer progression.

The downregulated PD-L1 indicates the delivery system can reverse cancer immunosuppression.

This investigation provides a facile strategy to overcome cancer MDR and immunosuppression.

Cholic acid cored star poly(DL-lactide) is featured by a rapid degradation rate with a surface erosion characteristic. TPGS not only reverses tumor drug resistance through downregulating P-gp expression of tumor cells but also enhances the anti-tumor efficiency through combined TPGS/CUR therapeutic actions on reversal of tumor immunosuppression mediated by CD47 and PD-L1. As compared with the CUR loaded nanoparticles without TPGS decoration, [email protected] with TPGS decoration results in significantly enhanced intracellular drug accumulation to efficiently induce cell apoptosis in drug resistant tumor cells.

More importantly, [email protected] possesses considerably improved efficacy in upregulating p53 and p21 as well as downregulating β-catenin, MMP-9, Snail, CD47 and PD-L1, indicating the TPGS decorated drug delivery system inhibits tumor development and metastasis much more efficiently.

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Article information: Ying-Ying Guan, Shao-Qi Zeng, Yin Qin, Yan Mu, Hong Liu, Vitamin E-tocopheryl polyethylene glycol succinate decorated drug delivery system with synergistic antitumor effects to reverse drug resistance and immunosuppression, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2021. https://doi.org/10.1016/j.colsurfa.2021.127387.

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