Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro

• Published in: Cancer Nanotechnology
• Main Authors: Pisano, Simone, Wang, Xiong, Jezabel Garcia Parra, Gazze, Andrea, Edwards, Kadie, Feltracco, Veronica, Hu, Yanzhen, He, Le, Gonzalez, Deyarina, Lewis, Francis, Conlan, Robert Steven, Li, Chao
• Format: Web Resource
• Language: English
• Published: Durham Research Square 05.11.2020
• Subjects: Cancer; Epigenetics
• DOI: 10.21203/rs.3.rs-50247/v3

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 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h 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 upregulate 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.