Self-assembled vesicles containing podophyllotoxin covalently modified with polyoxometalates for antitumor therapy

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Abstract
A wide variety of polyoxometalates (POMs) have been shown to have anti-tumor activity. The hydrophobic anticancer medicine podophyllotoxin (PPT) and the hydrophilic anticancer drug POMs are combined to create the amphiphilic drug PPT-POM-PPT. PPT-POM-PPT has the ability to self-assemble into hollow vesicles. Important properties of these vesicles, such as the critical aggregation concentration, have been identified. These vesicles have low hemolytic activity and high stability. The cytotoxicity test shows that PPT-POM-PPT vesicles have strong anti-tumor activity against lung and liver cancer cells and are safe for normal cells. Cell uptake experiments confirm that PPT-POM-PPT vesicles could effectively enter tumor cells and co-locate with lysosomes. PPT-POM-PPT vesicles exhibit synergistic effects of PPT and POMs, and the vesicles can easily penetrate cell membranes and be efficiently taken up by tumor cells, thus exerting antitumor effects. PPT-POM-PPT vesicles are both the carrier and the active drug ingredient, avoiding the potential risk of introducing additional carrier ingredients and allowing efficient drug delivery. The innovative use of the anti-cancer properties of POMs and PPT to construct amphiphilic self-assembly vesicles provides a theoretical basis and a new idea for the clinical application of POMs in cancer therapy.

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