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基于红色发光金纳米簇修饰褶皱 MXene 纳米片的临床前安全性评估:用于影像引导光热治疗的强强联合。

Preclinical safety assessment of red emissive gold nanocluster conjugated crumpled MXene nanosheets: a dynamic duo for image-guided photothermal therapy.

机构信息

Centre for Research in Nano Technology & Science (CRNTS), Sophisticated Analytical Instrument Facility (SAIF), IIT Bombay, Powai, Mumbai, 400076, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai, 400076, India.

出版信息

Nanoscale. 2023 Feb 9;15(6):2932-2947. doi: 10.1039/d2nr05773e.

DOI:10.1039/d2nr05773e
PMID:36692237
Abstract

Red emissive gold nanoclusters have potential as biological fluorescent probes, but lack sufficient light-to-heat conversion efficiency for photothermal therapy (PTT). MXene nanomaterials, on the other hand, have shown promise in PTT due to their strong near-infrared absorption abilities, but their instability caused by restacking of the sheets can decrease their available surface area. One approach to address this issue is to design sheets with wrinkles or folds. However, the crumpled or 3D MXene materials reported in the literature are actually aggregates of multiple nanosheets rather than a single sheet that is folded. In this study, a modified method for crumpling a single MXene sheet and further conjugating it with red emissive gold nanoclusters and folic acid was developed. A detailed toxicity study was performed in various cell lines and cellular uptake in cancer cells was studied using AFM to understand its interaction at the nano-bio interface. The material also demonstrated excellent utility as a bioimaging and PTT agent , with its high fluorescence allowing bioimaging at a lower concentration of 12 μg mL and a photothermal conversion efficiency of 43.51%. analyses of the cell death mechanisms induced by PTT were conducted through studies of apoptosis, cell proliferation, and ROS production. acute toxicity tests were conducted on male and female Wistar rats through oral and intravenous administration (20 mg kg dose), and toxicity was evaluated using various measures including body weight, hematology, serum biochemistry, and H&E staining. The findings from these studies suggest that the MXene gold nanoconjugate could be useful in a range of biomedical applications, with no observed toxicity following either oral or intravenous administration.

摘要

红色发光金纳米团簇有望成为生物荧光探针,但光热治疗(PTT)的光热转换效率不足。另一方面,MXene 纳米材料由于其强近红外吸收能力在 PTT 中显示出应用前景,但由于片层的堆积而导致的不稳定性会降低其可用表面积。解决这个问题的一种方法是设计具有褶皱或折痕的片层。然而,文献中报道的皱缩或 3D MXene 材料实际上是多个纳米片的聚集体,而不是单个折叠的纳米片。在这项研究中,开发了一种改进的方法来皱缩单个 MXene 片层,并进一步将其与红色发光金纳米团簇和叶酸进行共轭。在各种细胞系中进行了详细的毒性研究,并通过原子力显微镜(AFM)研究了其在癌细胞中的细胞摄取,以了解其在纳米生物界面的相互作用。该材料还表现出作为生物成像和 PTT 剂的优异实用性,其高荧光允许在较低浓度 12 μg mL 的情况下进行生物成像,光热转换效率为 43.51%。通过研究细胞凋亡、细胞增殖和 ROS 产生,对 PTT 诱导的细胞死亡机制进行了分析。通过口服和静脉给药(20mgkg 剂量)对雄性和雌性 Wistar 大鼠进行了急性毒性试验,并通过体重、血液学、血清生化和 H&E 染色等各种措施评估了毒性。这些研究的结果表明,MXene 金纳米复合物在各种生物医学应用中可能很有用,无论是口服还是静脉给药,都没有观察到毒性。

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