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多糖促进的生物合成制备 pH 响应型荧光金纳米簇作为一种生物相容性的肿瘤成像探针。

Polysaccharide enabled biogenic fabrication of pH sensing fluorescent gold nanoclusters as a biocompatible tumor imaging probe.

机构信息

Laboratory of Biopharmaceuticals & Nanomedicine, Division of Cancer Research, Regional Cancer Centre (Research Centre, University of Kerala), Thiruvananthapuram, Kerala, 695011, India.

Chemical Sciences & Technology Division, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Thiruvananthapuram, Kerala, 695019, India.

出版信息

Mikrochim Acta. 2020 Mar 25;187(4):246. doi: 10.1007/s00604-020-4189-8.

Abstract

A biocompatible natural polysaccharide (PSP001) isolated from the fruit rind of Punica granatum was conjugated with L-cysteine (Y) to be used as a skeleton for the fabrication of fluorescent gold nanoclusters (AuNCs) represented as PSP-Y-AuNCs. With an average size of ~ 6 nm, PSP-Y-AuNCs demonstrated high quantum yield (31%), with a pH-sensitive fluorescence emission behavior. An emission maximum of 520 nm was obtained at acidic pH, which was blue shifted with increasing pH. This feature provides the possibilities for accurate ratiometric pH imaging. The PSP-Y-AuNCs not only demonstrated excellent biocompatibility with cancer cells and isolated peripheral lymphocytes and red blood cells but also demonstrated to be an active molecular imaging probe with appealing cellular uptake efficiency. The investigations with BALB/c mice further confirmed the non-toxic nature and in vivo imaging potential of the AuNCs. Estimation of the bio-distribution on solid tumor bearing syngeneic murine models revealed a tumor-targeted enhanced fluorescence emission pattern which is attributed to the pH responsive fluorescence behavior and the acidic microenvironment of the tumor. These findings were further confirmed with an impressive tumor accumulation pattern displayed in a xenograft of human cancer bearing nude mice. On account of their impressive biocompatibility and photophysical features, PSP-Y-AuNCs can exploited for the real-time fluorescence imaging of cancer tissues. Graphical abstract Fluorescent gold nanoclusters (PSP-Y-AuNCs) fabricated using a non-toxic natural polysaccharide (PSP001) demonstrated pH sensitive fluorescence emission pattern. The increased fluorescence readouts at acidic conditions and excellent biocompatibility made the PSP-Y-AuNCs an appealing candidate for in vivo tumor imaging applications.

摘要

一种从石榴果皮中分离得到的生物相容性天然多糖(PSP001)与 L-半胱氨酸(Y)偶联,用作制备荧光金纳米簇(AuNCs)的骨架,记为 PSP-Y-AuNCs。PSP-Y-AuNCs 的平均尺寸约为~6nm,具有高量子产率(31%)和对 pH 敏感的荧光发射行为。在酸性 pH 下,获得了 520nm 的发射最大值,随着 pH 的增加,发射峰发生蓝移。这一特性为准确的比率 pH 成像提供了可能性。PSP-Y-AuNCs 不仅表现出与癌细胞、分离的外周淋巴细胞和红细胞优异的生物相容性,而且还表现出作为一种有吸引力的细胞摄取效率的活性分子成像探针。在 BALB/c 小鼠中的研究进一步证实了 AuNCs 的无毒性质和体内成像潜力。在荷瘤同基因小鼠模型上进行的生物分布估计揭示了一种肿瘤靶向增强的荧光发射模式,这归因于 pH 响应荧光行为和肿瘤的酸性微环境。在荷有人源癌症的裸鼠异种移植模型中,进一步证实了令人印象深刻的肿瘤积累模式。由于其令人印象深刻的生物相容性和光物理特性,PSP-Y-AuNCs 可用于癌症组织的实时荧光成像。

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