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• W4307900470 abstract "Cholesterol and its metabolites act as important signaling molecules that promote tumor development. In recent years, increasing evidence has indicated that targeting cholesterol biosynthesis, metabolism, and membrane distribution could potentially sensitize cancer cells to chemotherapy. However, because of the lack of selectivity and the large differences in half-life, metabolism, and clearance between drugs, combining cholesterol inhibitors with chemotherapy agents can produce toxic side effects and contradictory results, making this kind of treatment highly controversial. Here, we developed a PPI-based multifunctional liposome system to effectively cope with the above challenges. As a steroidal saponin, PPI acts as a membrane stabilizer to replace the cholesterol needed to form liposomes, avoiding the shortcomings caused by extra cholesterol intake. Moreover, as a chemotherapy adjuvant, PPI has great potential to interfere with cancer-derived cholesterol disorders, exerting a cholesterol-lowering effect as strong as lovastatin. The expression of important cholesterol synthesis-related proteins, SOAT1, HMGCR, and SREBP2, were only 1/3-1/2 of lovastatin. In addition, by forming complexes with membrane cholesterol, PPI not only improves plasma membrane fluidity and permeability but also disrupt the distribution of lipid rafts, which decreased the expression of ABC transporters to 0.6–1.0-fold, allowing more chemotherapy agents to reach the intracellular targets. Finally, PPI-DOX co-loaded liposomes (DLPs) exhibited stronger tumor inhibition effect in in vivo animal studies, which was 1.3-fold that of Chol-DOX-LP. Therefore, PPI-based liposomes offer a new strategy and opportunity for cancer treatment by combining cancer-derived cholesterol modulation with other anti-cancer therapies." @default.
• W4307900470 created "2022-11-06" @default.
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• W4307900470 date "2022-12-01" @default.
• W4307900470 modified "2023-10-18" @default.
• W4307900470 title "A novel polyphyllin I-based liposome delivery system sensitizes hepatic carcinoma to doxorubicin via cholesterol modulation" @default.
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• W4307900470 doi "https://doi.org/10.1016/j.jddst.2022.103925" @default.
• W4307900470 hasPublicationYear "2022" @default.
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