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pH 响应性藜芦酸载多聚多巴胺纳米粒子对人三阴性乳腺癌细胞的抗增殖和凋亡作用。

Antiproliferative and Apoptotic Effects of pH-Responsive Veratric Acid-Loaded Polydopamine Nanoparticles in Human Triple Negative Breast Cancer Cells.

机构信息

Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India.

出版信息

Chem Biodivers. 2023 Jun;20(6):e202201006. doi: 10.1002/cbdv.202201006. Epub 2023 May 19.

DOI:10.1002/cbdv.202201006
PMID:37140976
Abstract

Veratric acid (VA) is plant-derived phenolic acid known for its therapeutic potential, but its anticancer effect on highly invasive triple-negative breast cancer (TNBC) is yet to be evaluated. Polydopamine nanoparticles (nPDAs) were chosen as the drug carrier to overcome VA's hydrophobic nature and ensure a sustained release of VA. We prepared pH-sensitive nano-formulations of VA-loaded nPDAs and subjected them to physicochemical characterization and in vitro drug release studies, followed by cell viability and apoptotic assays on TNBC cells (MDA-MB-231 cells). The SEM and zeta analysis revealed spherical nPDAs were uniform size distribution and good colloidal stability. In vitro drug release from VA-nPDAs was sustained, prolonged and pH-sensitive, which could benefit tumor cell targeting. MTT and cell viability assays showed that VA-nPDAs (IC50=17.6 μM) are more antiproliferative towards MDA-MB-231 cells than free VA (IC50=437.89 μM). The induction of early and late apoptosis by VA-nPDAs in the cancer cells was identified using annexin V and dead cell assay. Thus, the pH response and sustained release of VA from nPDAs showed the potential to enter the cell, inhibit cell proliferation, and induce apoptosis in human breast cancer cells, indicating the anticancer potential of VA.

摘要

藜芦酸(VA)是一种植物来源的酚酸,具有治疗潜力,但它对高度侵袭性的三阴性乳腺癌(TNBC)的抗癌作用尚未得到评估。选择聚多巴胺纳米粒子(nPDAs)作为药物载体,以克服 VA 的疏水性并确保 VA 的持续释放。我们制备了负载 VA 的 nPDAs 的 pH 敏感纳米制剂,并对其进行了物理化学特性和体外药物释放研究,然后对 TNBC 细胞(MDA-MB-231 细胞)进行细胞活力和凋亡测定。SEM 和 zeta 分析显示,球形 nPDAs 具有均匀的粒径分布和良好的胶体稳定性。从 VA-nPDAs 中释放的 VA 是持续的、延长的和 pH 敏感的,这有利于肿瘤细胞靶向。MTT 和细胞活力测定表明,VA-nPDAs(IC50=17.6 μM)对 MDA-MB-231 细胞的增殖抑制作用强于游离 VA(IC50=437.89 μM)。用 annexin V 和死细胞测定法鉴定了 VA-nPDAs 在癌细胞中诱导的早期和晚期凋亡。因此,nPDAs 中 VA 的 pH 响应和持续释放显示出进入细胞、抑制细胞增殖和诱导人乳腺癌细胞凋亡的潜力,表明 VA 具有抗癌潜力。

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