Folate-targeting annonaceous acetogenins nanosuspensions: significantly enhanced antitumor efficacy in HeLa tumor-bearing mice |
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| Authors: | Haowen Li Yijing Li Hui Ao Dongdong Bi Meihua Han Yifei Guo |
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| Affiliation: | 1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &2. Peking Union Medical College, Beijing, P. R. China |
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| Abstract: | Annonaceous acetogenins (ACGs) are one of the most active constituents isolated from Annona species with potent antitumor activity. However, the poor solubility and severe side effect greatly limit their use in clinic. In this study, folic acid (FA) modified annonaceous acetogenins nanosuspensions (FA-PEG-ACGs-NSps) had been successfully prepared using DSPE-PEG-FA and soybean lecithin (SPC) as stabilizers. The resultant FA-PEG-ACGs-NSps had a mean particle size of 119.7?nm, a zeta potential of –23.0?mV and a high drug payload of 49.68%. The obtained ACGs-NSps had a good stability in various physiological media, and showed sustained drug release. Compared to common ACGs nanoparticles (PEG-ACGs-NSps), FA-PEG-ACGs-NSps showed significantly enhanced in vitro cytotoxicity against folate receptor-positive HeLa cell lines (IC50, 0.483?μg/mL vs. 0.915?μg/mL, p?In vivo experiments demonstrated that FA-PEG-ACGs-NSps brought more drug molecules into tumors and greatly improved the antitumor efficacy (TIR, 76.45% vs. 25.29%, p?
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| Keywords: | Annonaceous acetogenins folate targeting nanosuspensions DSPE-PEG-FA PEGylation anti-tumor efficiency |
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