Abstract
BackgroundAmphiphilic 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.ResultsFollowing 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.ConclusionsThis study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.
Highlights
Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues
Nanomicelles showed a rounded shape and both empty (Fig. 1a) and Suberoylanilide hydroxamic acid (SAHA)-loaded (Fig. 1b) nanomicelles presented a diameter of 32 nm
Here, we have demonstrated that the histone deacetylase inhibitor SAHA can be effectively encapsulated in pluronic nanoparticles
Summary
Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. These platforms have a broad applicability in cancer treatment. 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. The use of MCF-7 and HeLa for breast and cervical cancer studies involving epigenetic drugs is well established due to the high genetic variability of these cells lines that could be tackled by such an approach (Landry et al 2013; Zhou et al 2019)
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