Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran 13185/768, Iran.
Biomedical Engineering Department, Amirkabir University of Technology (Tehran Polytechnic), Tehran 1591634311, Iran.
Life Sci. 2021 Aug 15;279:119576. doi: 10.1016/j.lfs.2021.119576. Epub 2021 May 6.
Cancer-targeted co-delivery of therapeutic agents has been recognized as an effective strategy for increasing efficacy and reducing side effects of therapeutic agents. In this study, we used methotrexate (MTX) alone as a targeting moiety and chemotherapeutic agent and in combination with docetaxel (DTX) and doxorubicin (DOX) as chemotherapeutic agents to stop cancer cell proliferation with the aid of newly designed nanostructured lipid carriers (NLCs). The physicochemical properties of our designed nanocomplexes were evaluated by DLS, FT-IR spectroscopy, SEM, and TEM. Moreover, the targeting efficiency of the designed and synthesized nanoplatforms was evaluated on the folate receptor (FR) positive human breast cancer cell line (MCF-7) and FR negative human alveolar basal epithelial cells (A549). The NLCs/DTX/DOX/CS and NLCs/DTX/DOX/CS-MTX complexes significantly increased the cell cytotoxicity and the cell apoptosis rate. However, the complexes significantly reduced the capability of colony formation and cell migration. Our results revealed that NLCs/DTX/DOX/CS-MTX had synergistic cytotoxicity, reactive oxygen spaces, autophagy, and the apoptosis induction ability with an enhanced cellular internalization rate in FR-positive cancer cells, thorough MTX recognition capability. We conclude that the NLCs/DTX/DOX/CS-MTX complex is a new promising paradigm for breast cancer-targeted co-delivery.
癌症靶向联合递药已被认为是提高治疗药物疗效和降低其副作用的有效策略。在这项研究中，我们单独使用甲氨蝶呤（MTX）作为靶向部分和化疗药物，并与多西他赛（DTX）和阿霉素（DOX）联合使用，借助新设计的纳米结构脂质载体（NLCs）来阻止癌细胞增殖。我们通过 DLS、FT-IR 光谱、SEM 和 TEM 评估了所设计的纳米复合物的理化性质。此外，还评估了设计和合成的纳米平台在叶酸受体（FR）阳性人乳腺癌细胞系（MCF-7）和 FR 阴性人肺泡基底上皮细胞（A549）上的靶向效率。NLCs/DTX/DOX/CS 和 NLCs/DTX/DOX/CS-MTX 复合物显著提高了细胞毒性和细胞凋亡率。然而，这些复合物显著降低了集落形成和细胞迁移的能力。我们的结果表明，NLCs/DTX/DOX/CS-MTX 具有协同细胞毒性、活性氧空间、自噬和凋亡诱导能力，并通过 FR 阳性癌细胞的增强细胞内化率和 MTX 的识别能力，具有增强的细胞内化率。我们得出结论，NLCs/DTX/DOX/CS-MTX 复合物是一种有前途的乳腺癌靶向联合递药的新范例。
