ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy.

ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy.
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DOI:
10.1021/acsomega.1c04909
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发表时间:
2021-12-28
期刊:
影响因子:
4.1
通讯作者:
Ma X
Ma X
中科院分区:
化学3区
文献类型:
--
作者:
Pan W;Chen W;Min Y;Wang J;Yang Z;Xu T;Yu F;Shen G;Hu Y;Ma X

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吲哚菁绿(ICG)已应用于各种手术导航系统,在术中影像诊断中发挥着重要作用。然而,光稳定性差和肿瘤靶向能力不理想限制了其广阔的应用前景。几十年来,构建用于肿瘤靶向诊断和治疗的纳米药物递送系统已成为研究热点。黑磷纳米片(BPNS)作为一种新型可生物降解纳米材料,与其他已报道的二维(2D)纳米材料相比,具有高负载量、良好的生物相容性、肿瘤靶向性和光热效应等优点。在此,构建了负载ICG的聚乙二醇(PEG)修饰的BPNS(ICG@BPNS-PEG)纳米复合材料,以提高肿瘤靶向能力并通过实时荧光成像指导光热治疗。本研究成功构建了合适尺寸(240±28 nm)的ICG@BPNS-PEG纳米复合材料。经过四个近激光照射(NIR)开关循环后,ICG@BPNS-PEG 纳米复合材料的光稳定性超过了游离 ICG。此外,ICG@BPNS-PEG纳米复合材料具有增强的光热转换能力。流式细胞术的细胞摄取结果表明,ICG@BPNS-PEG纳米复合材料由于合适的尺寸和被动的细胞摄取而易于吞咽。此外,通过MTT法对MCF-7、4T1乳腺癌细胞和健康RPE细胞的细胞毒性评价表明,ICG@BPNS-PEG纳米复合材料在无需辐照的情况下具有较低的细胞毒性和良好的细胞相容性。然而,细胞毒性和活/死染色证明ICG@BPNS-PEG纳米复合材料在辐照下具有令人满意的光热治疗效果。在携带4T1的小鼠模型中,静脉注射纳米复合材料后的荧光成像表明,与游离ICG相比,ICG@BPNS-PEG纳米复合材料通过增强渗透性和保留(EPR)效应具有优异的被动肿瘤靶向积累能力。此外,与其他组相比,肿瘤体积的变化显示出显着的肿瘤生长抑制效果。此外,4T1小鼠主要器官的苏木精-伊红(H&E)染色结果也表明纳米复合材料具有良好的生物相容性。因此,构建的ICG@BPNS-PEG纳米复合材料在乳腺癌治疗中具有巨大潜力。
Indocyanine green (ICG) has been used in various surgical navigation systems and plays an important role in intraoperative imaging diagnosis. However, the poor photostability and unsatisfactory tumor-targeting ability have limited its broad application prospects. In the decades, the construction of a nanodrug delivery system for tumor-targeting diagnosis and therapy has become a research hotspot. Black phosphorus nanosheets (BPNS), as a new kind of biodegradable nanomaterials, have the advantages of high loading capacity, good biocompatibility, tumor targeting, and photothermal effect over other two-dimensional (2D) reported nanomaterials. Herein, ICG-loaded poly(ethylene glycol) (PEG)-modified BPNS (ICG@BPNS-PEG) nanocomposites are constructed to improve the tumor-targeting capacity and guide photothermal therapy through real-time fluorescence imaging. In this study, ICG@BPNS-PEG nanocomposites with a suitable size (240 ± 28 nm) have been successfully constructed. The photostability of ICG@BPNS-PEG nanocomposites surpassed that of free ICG after four on–off cycles of near laser irradiation (NIR). Moreover, ICG@BPNS-PEG nanocomposites have enhanced photothermal conversion ability. The cellular uptake result through flow cytometry showed that ICG@BPNS-PEG nanocomposites could be swallowed easily owing to the suitable size and passive cellular uptake. In addition, the cytotoxicity evaluation of MCF-7, 4T1 breast cancer cells, and healthy RPE cells through the MTT assay demonstrated that ICG@BPNS-PEG nanocomposites have lower cytotoxicity and good cellular compatibility without irradiation. However, the cytotoxicity and live/dead staining proved that ICG@BPNS-PEG nanocomposites have satisfactory photothermal therapeutic effects when irradiated. In the 4T1-bearing mice model, the fluorescence imaging after intravenous injection of nanocomposites showed that ICG@BPNS-PEG nanocomposites have superior passive tumor targeting accumulation through the enhanced permeability and retention (EPR) effect compared with that of free ICG. Also, changes in tumor volume showed a remarkable tumor growth inhibition effect compared with other groups. Moreover, the results of hematoxylin–eosin (H&E) staining of major organs in 4T1-bearing mice also demonstrated that the nanocomposites have good biocompatibility. Therefore, the constructed ICG@BPNS-PEG nanocomposites have substantial potential in breast cancer therapy.
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