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首页> 外文期刊>ACS applied materials & interfaces >Carboplatin-Loaded, Raman-Encoded, Chitosan-Coated Silver Nanotriangles as Multimodal Traceable Nanotherapeutic Delivery Systems and pH Reporters inside Human Ovarian Cancer Cells
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Carboplatin-Loaded, Raman-Encoded, Chitosan-Coated Silver Nanotriangles as Multimodal Traceable Nanotherapeutic Delivery Systems and pH Reporters inside Human Ovarian Cancer Cells

机译:装载卡铂,拉曼编码,壳聚糖涂层银纳米前方作为多峰可追踪的纳米治疗递送系统和人类卵巢癌细胞内的愈合症

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摘要

Ovarian cancer is a common cause of cancer death in women and is associated with the highest mortality rates of all gynecological malignancies. Carboplatin (CBP) is the most used cytotoxic agent in the treatment of ovarian cancer. Herein, we design and assess a CBP nanotherapeutic delivery system which allows combinatorial functionalities of chemotherapy, pH sensing, and multimodal traceable properties inside live NIH:OVCAR-3 ovarian cancer cells. In our design, a pH-sensitive Raman reporter, 4-mercaptobenzoic acid (4MBA) is anchored onto the surface of chitosan-coated silver nanotriangles (chit-AgNTs) to generate a robust surface-enhanced Raman scattering (SERS) traceable system. To endow this nanoplatform with chemotherapeutic abilities, CBP is then loaded to 4MBA-labeled chit-AgNTs (4MBA-chit-AgNTs) core under alkaline conditions. The uptake and tracking potential of CBP-4MBA-chit-AgNTs at different Z-depths inside live ovarian cancer cells is evaluated by dark-field and differential interference contrast (DIC) microscopy. The ability of CBP-4MBA-chit-AgNTs to operate as near-infrared (NIR)-responsive contrast agents is validated using two noninvasive techniques: two-photon (TP)-excited fluorescence lifetime imaging microscopy (FLIM) and confocal Raman microscopy (CRM). The most informative data about the precise localization of nanocarriers inside cells correlated with intracellular pH sensing is provided by multivariate analysis of Raman spectra collected by scanning CRM. The in vitro cell proliferation assay clearly shows the effectiveness of the prepared nanocarriers in inhibiting the growth of NIH:OVCAR-3 cancer cells. We anticipate that this class of nanocarriers holds great promise for application in image-guided ovarian cancer chemotherapy.
机译:卵巢癌是癌症死亡的常见原因,与所有妇科恶性肿瘤的最高死亡率有关。 Carboplatin(CBP)是治疗卵巢癌中最常用的细胞毒剂。在此,我们设计和评估CBP纳米治疗输送系统,其允许在Live NIH:OVCAR-3卵巢癌细胞中组合化疗,pH感测和多模式可追踪性能的组合官能团。在我们的设计中,pH敏感的拉曼记者,4-巯基苯甲酸(4MBA)锚定到壳聚糖涂覆的银纳米前(CHIT-AGNT)的表面上,以产生稳健的表面增强拉曼散射(SERS)可追踪系统。为了赋予化学治疗能力的纳米纳米,然后在碱性条件下将CBP加载到4MBA标记的Chit-Agnts(4MBA-Chit-Agnts)核。通过暗场和微分干扰对比度(DIC)显微镜评估不同Z-DISTINGS的CBP-4MBA-CHIT-AGNTS的摄取和跟踪电位。 CBP-4MBA-CHIT-AGS作为近红外线(NIR) - 响应造影剂的能力使用两种非侵入性技术进行验证:双光子(TP) - 渗透荧光寿命成像显微镜(FLIM)和共聚焦拉曼显微镜( CRM)。通过扫描CRM收集的拉曼光谱的多变量分析提供了关于与细胞内pH感测相关的细胞内纳米载波的精确定位的最佳信息。体外细胞增殖测定清楚地显示了制备的纳米载体在抑制NIH:OVCAR-3癌细胞生长方面的有效性。我们预计这类纳米庭园是在图像引导卵巢癌化疗中的应用持久的承诺。

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