Salas-Huenuleo Edison, Hernández Andrea, Lobos-González Lorena, Polakovičová Iva, Morales-Zavala Francisco, Araya Eyleen, Celis Freddy, Romero Carmen, Kogan Marcelo J
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380000, Chile.
Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.
Pharmaceutics. 2022 Apr 28;14(5):958. doi: 10.3390/pharmaceutics14050958.
One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.
恢复下调的微小RNA是近年来一种有吸引力的癌症治疗方法。它们在细胞增殖、分化、存活、凋亡、细胞周期、血管生成和转移等细胞过程中发挥着重要的多调节作用。在本研究中，设计并合成了一种载有miR-145的金纳米平台（GNPF），miR-145是包括上皮性卵巢癌在内的多种癌症类型中下调的微小RNA。为了实现靶向目的，GNPF用FSH33肽进行功能化，该肽对卵巢癌具有选择性，并装载miR-145以获得纳米系统GNPF-miR-145。GNPF-mir-145被选择性地纳入A2780和SKOV3细胞中，显著抑制细胞活力和迁移，并表现出增殖和非锚定依赖性生长能力。此外，它通过破坏细胞膜减少了VEGF的释放，减小了卵巢癌球体的大小，从而降低细胞活力并可能激活细胞凋亡。这些结果为使用纳米颗粒作为选择性载体开发基于miR的疗法提供了重要进展，并为体内评估提供了方法。
