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Several polyoxometalates (POMs) have been shown to possess antitumor activity. In this study, hydrophilic POMs were combined with the hydrophobic drug podophyllotoxin (PPT) to create an amphiphilic anti-cancer drug PPT-POM-PPT, which can self-assemble into hollow vesicles. The properties of these vesicles, such as the critical aggregation concentration, were characterized. These vesicles had low hemolytic activity and high stability. Cytotoxicity tests showed that the PTT-POM-PPT vesicles exhibit strong antitumor activity against lung and liver cancer cells without significantly affecting normal cells. Cell uptake experiments confirm that the PPT-POM-PPT vesicles can easily penetrate cell membranes and effectively enter tumor cells, thus exerting anti-tumor effects. Furthermore, these vesicles co-localized with lysosomes. Moreover, these PPT-POM-PPT vesicles exhibit synergistic effects of PPT and POMs. They are efficient drug delivery platforms that act as both the carrier and the active drug, avoiding the potential risks associated with additional carrier ingredients. In summary, due to their anticancer properties, POMs and PPT facilitate the generation of novel amphiphilic self-assembling vesicles, providing a theoretical basis and enabling clinical applications of POMs in cancer therapy.

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