Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro
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RESEARCH
Cancer Nanotechnology Open Access
Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro S. Pisano1,2† , X. Wang3,4,5†, J. Garcia‑Parra1, A. Gazze1, K. Edwards1, V. Feltracco1, Y. Hu3,4, L. He4, D. Gonzalez1, L. W. Francis1, R. S. Conlan1 and C. Li4* *Correspondence: [email protected] † S. Pisano and X. Wang have contributed equally to the work 4 Xi’an Jiaotong University Suzhou Academy, Suzhou 215123, People’s Republic of China Full list of author information is available at the end of the article
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 nanomi‑ celles were prepared using a thin-film drying method and characterized for size, sur‑ face 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 nanomi‑ celles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression. Keywords: Pluronic, Drug delivery, Nanomicelles, Epigenetic drugs, Cancer, SAHA
Background Chemical compounds directly targeting epigenetic processes have emerged as potential treatments for metastatic disease (Fardi et al. 2018). Epigenetics involves alterations to the DNA and chromatin landscape and consequently gene expression patterns and biological processes (Dupont et al. 2009). The molecular alterations to the nucleosomeforming histone proteins are one of the major epigenetic modifications that have been found to be altered in cancer (Audia and Campbell 2016). Compounds targeting these modifications, reverting them to a non-cancer state, have great therapeutic potential. Suberoylanilide Hydroxamic Acid (SAHA, commercially known as Vorinostat)
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