Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro

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Abstract

Background: Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA-loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content, and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell cycle and markers of cancer progression. Results: Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA-loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30 nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72 h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to up-regulate E-cadherin expression, potentially influencing tumor migration. Conclusions: This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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Pisano, S., Wang, X., Garcia-Parra, J., Gazze, A., Edwards, K., Feltracco, V., … Li, C. (2020). Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro. Cancer Nanotechnology, 11(1). https://doi.org/10.1186/s12645-020-00070-8

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