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. 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. 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.

中文翻译：

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Nanomicelles增强组蛋白脱乙酰基酶抑制剂的体外功效

用作纳米胶束药物载体的两亲性嵌段共聚物可以有效克服不良的药物溶解性和特异性问题。因此，这些平台在癌症治疗中具有广泛的适用性。在这项研究中，Pluronic F127用于制造包含组蛋白脱乙酰基酶抑制剂SAHA的纳米胶束，该胶束在多种肿瘤类型中具有表观遗传学驱动的抗癌作用。使用薄膜干燥方法制备了加载SAHA的纳米胶束，并对其尺寸，表面电荷，药物含量和药物释放特性进行了表征。测试了负载颗粒的体外活性及其对细胞周期和癌症进展标志物的影响。经过详细的颗粒表征，细胞增殖实验表明，与游离药物制剂相比，装有SAHA的纳米胶束能更有效地抑制HeLa和MCF-7细胞系的生长。包含30 nm SAHA的纳米颗粒能够在72小时的时间内释放高达100％的封装药物。此外，基因和蛋白质表达分析表明它们的细胞减少作用是通过调节p21和p53表达来实现的。SAHA还显示出上调E-钙黏着蛋白表达，可能影响肿瘤迁移。这项研究强调了利用基于普卢尼克的纳米胶束来输送调节表观遗传过程从而抑制癌症发展和进程的化合物的机会。包含30 nm SAHA的纳米颗粒能够在72小时的时间内释放高达100％的封装药物。此外，基因和蛋白质表达分析表明它们的细胞减少作用是通过调节p21和p53表达来实现的。SAHA还显示出上调E-钙黏着蛋白表达，可能影响肿瘤迁移。这项研究强调了利用基于普卢尼克的纳米胶束来输送调节表观遗传过程从而抑制癌症发展和进程的化合物的机会。包含30 nm SAHA的纳米颗粒能够在72小时的时间内释放高达100％的封装药物。此外，基因和蛋白质表达分析表明它们的细胞减少作用是通过调节p21和p53表达来实现的。SAHA还显示出上调E-钙黏着蛋白表达，可能影响肿瘤迁移。这项研究强调了利用基于普卢尼克的纳米胶束来输送调节表观遗传过程从而抑制癌症发展和进程的化合物的机会。