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首页> 美国卫生研究院文献>Nanotheranostics >Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer
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Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer

机译：聚多巴胺涂层金纳米星用于多药耐药性乳腺癌的联合抗肿瘤和抗血管生成治疗

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Cancer combination therapy can improve treatment efficacy and is widely utilized in the biomedical field. In this paper, we propose a facile strategy to develop a polydopamine (PDA)-coated Au nanostar (NS@PPFA) as a multifunctional nanoplatform for cancer targeting and combination therapy. The Au nanostar demonstrated high photothermal conversion efficiency because of the tip-enhanced plasmonic effect. Modification of PDA and folic acid on the NS surface improved its drug-loading efficiency and targeting capability. In vitro, compared with nontargeted cells, targeted breast cancer MCF-7 cells demonstrated efficient uptake of chemodrug-loaded NS-D@PPFA through the receptor-mediated endocytosis pathway. In combination with the photothermal effect induced by near-infrared laser irradiation, controlled payload release could be activated in response to both internal (acid) and external (photothermal) stimuli, leading to an efficient chemo-photothermal action against MCF-7 cells and drug-resistant MCF-7/ADR cells. By contrast, cellular damage was less obvious in normal HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts). In addition, payload-free NS@PPFA exhibited a high binding affinity (Kd = 2.68 × 10-10 M) toward vascular endothelial growth factor (VEGF-A165), which was at least two orders of magnitude stronger than that of highly abundant plasma proteins, such as human serum albumin. Furthermore, in vitro study showed that NS@PPFA could effectively inhibit VEGF-A165-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells, resulting in additional therapeutic benefits for eradicating tumors through a simultaneous antiangiogenic action in chemo-photothermal treatment. The combined treatment also exhibited the lowest microvessel density, leading to a potent antitumor effect in vivo. Overall, our “all-in-one” nanoplatform is highly promising for tumor therapy, enabling effective treatment against multidrug-resistant cancers.
机译：癌症联合疗法可以提高治疗效果，并在生物医学领域得到广泛应用。在本文中，我们提出了一种简便的策略来开发聚多巴胺（PDA）涂层的Au纳米星（NS @ PPFA）作为用于癌症靶向和联合治疗的多功能纳米平台。由于尖端增强的等离激元效应，金纳米星表现出高的光热转换效率。在NS表面修饰PDA和叶酸可提高其载药效率和靶向能力。在体外，与非靶向细胞相比，靶向乳腺癌MCF-7细胞通过受体介导的内吞途径证明了化学药物负载的NS-D @ PPFA的有效摄取。结合近红外激光辐照引起的光热效应，可以响应内部（酸）和外部（光热）刺激激活有效载荷释放，从而导致针对MCF-7细胞和药物的有效化学光热作用耐药MCF-7 / ADR细胞。相比之下，正常HaCaT（人类皮肤角质形成细胞）和NIH-3T3细胞（鼠成纤维细胞）的细胞损伤不那么明显。此外，无有效载荷的NS @ PPFA对血管内皮生长因子（VEGF-A165）的结合亲和力（Kd = 2.68×10 -10 M）高，至少为两个数量级。比高度丰富的血浆蛋白（例如人血清白蛋白）更强。此外，体外研究表明，NS @ PPFA可以有效抑制VEGF-A165诱导的人脐静脉内皮细胞的增殖，迁移和管形成，从而通过在化学光热治疗中同时具有抗血管生成作用，从而消除肿瘤的其他治疗益处。 。联合治疗还表现出最低的微血管密度，导致体内有效的抗肿瘤作用。总体而言，我们的“多合一”纳米平台在肿瘤治疗方面非常有前途，能够有效治疗多重耐药性癌症。

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