Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, CONICET, Santa Fe, Argentina; Área de Biocoloides y Nanotecnología, Instituto de Tecnología de Alimentos, Facultad de Ingeniería Química, Universidad Nacional del Litoral (ITA-FIQ-UNL), 1 de Mayo 3250, Santa Fe, 3000, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, CONICET, Santa Fe, Argentina; Centro de Medicina Comparada, Instituto de Ciencias Veterinarias del Litoral (ICiVet Litoral), Universidad Nacional del Litoral (UNL), Consejo Nacional de, Investigaciones Científicas y Técnicas (CONICET), R.P. Kreder 2805, Esperanza 3080, Argentina.
Colloids Surf B Biointerfaces. 2021 Aug;204:111777. doi: 10.1016/j.colsurfb.2021.111777. Epub 2021 Apr 20.
Antitumor activity of plant-derived flavonoids has been researched during recent decades. Among them, genistein (Gen) stands out for showing cytotoxic activity against breast cancer cells. However, its low water solubility, limited bioavailability, and fast metabolism hinder its administration in chemopreventive therapies. To overcome these obstacles, bovine serum albumin nanovehicles (BSAnp) were obtained by a heat-induced self-assembly process at 70 °C and two aqueous medium pH (9.0 and 11.0) and assayed for the Gen loading. Thus, in this work, Gen loading in BSAnp was studied by spectroscopic techniques and compared with the one obtained for its stereoisomer, chrysin (Chrys). Results revealed that Gen binds to BSAnp via fluorescence quenching mechanism forming inclusion complexes. Compared to Chrys, Gen binding to BSAnp involved more molecules, whereas the association constant was similar for both flavonoids. In general, flavonoid loading in protein systems was strongly affected by the combined effects of BSA conformational state (native vs. aggregated), nanovehicle size, and flavonoid chemical structure. To evaluate the antitumor properties freeze-dried powders were obtained, and they were assayed in vitro after reconstitution by XTT technique and Annexin V-FITC flow cytometry against mouse mammary adenocarcinoma F3II cells. Gen-loaded BSAnp produced a significant decrease in cell viability compared with unloaded BSAnp systems, being the highest cytotoxic effects found for the lowest sized Gen-loaded BSAnp. The leading cytotoxicity mechanism for Gen-loaded systems was apoptosis. Summarizing, it can be concluded that BSAnp constitute versatile nanovehicles for potential flavonoid incorporation in pharmaceutical and nutraceutical matrices.
近几十年来，人们一直在研究植物来源的类黄酮的抗肿瘤活性。其中，染料木黄酮（Gen）因其对乳腺癌细胞具有细胞毒性活性而引人注目。然而，其低水溶性、有限的生物利用度和快速代谢阻碍了其在化学预防疗法中的应用。为了克服这些障碍，通过在 70°C 下的热诱导自组装过程获得了牛血清白蛋白纳米载体（BSAnp），并在两种水介质 pH（9.0 和 11.0）下测定了 Gen 的负载量。因此，在这项工作中，通过光谱技术研究了 Gen 在 BSAnp 中的负载量，并将其与立体异构体白杨素（Chrys）的负载量进行了比较。结果表明，Gen 通过荧光猝灭机制与 BSAnp 结合形成包合物。与 Chrys 相比，Gen 与 BSAnp 的结合涉及更多的分子，而两种黄酮类化合物的结合常数相似。一般来说，黄酮类化合物在蛋白质体系中的负载量受到 BSA 构象状态（天然态与聚集态）、纳米载体大小和黄酮类化学结构的综合影响。为了评估抗肿瘤特性，获得了冻干粉末，并通过 XTT 技术和 Annexin V-FITC 流式细胞术在体外对其进行了重新构建后，对鼠乳腺腺癌 F3II 细胞进行了检测。与未负载 BSAnp 的系统相比，负载 Gen 的 BSAnp 显著降低了细胞活力，而最低载药量的 BSAnp 产生的细胞毒性作用最高。负载 Gen 的系统的主要细胞毒性机制是细胞凋亡。综上所述，可以得出结论，BSAnp 是一种多功能的纳米载体，可将潜在的黄酮类化合物掺入药物和营养基质中。
