基于部分还原氧化石墨烯纳米复合材料的肿瘤靶向光动力-光热联合治疗剂的制备

doi:10.7503/cjcu20180181

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (10): 2185.doi: 10.7503/cjcu20180181

基于部分还原氧化石墨烯纳米复合材料的肿瘤靶向光动力-光热联合治疗剂的制备

王雪丽^1,², 王振新²()

1. 吉林工商学院粮食学院, 长春 130507
2. 中国科学院长春应用化学研究所, 电分析化学国家重点实验室, 长春 130022

收稿日期:2018-02-07 出版日期:2018-09-29 发布日期:2018-09-29
作者简介:
联系人简介: 王振新, 男, 博士, 研究员, 博士生导师, 主要从事生物芯片研究和纳米粒子在多模态成像中的应用研究. E-mail: wangzx@ciac.ac.cn
基金资助:
国家自然科学基金(批准号: 21475126, 21775145)资助.

Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide^†

WANG Xueli^1,², WANG Zhenxin^2,^*()

1. Grain College, Jilin Business and Technology College, Changchun 130507, China
2. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry Chinese Academy of Science, Changchun 130022, China

Received:2018-02-07 Online:2018-09-29 Published:2018-09-29
Contact: WANG Zhenxin E-mail:wangzx@ciac.ac.cn
Supported by:
† Supported by the National Science Foundation of China(Nos.21475126, 21775145).

摘要/Abstract

摘要：

以氧化石墨烯(GO)为原料, 通过温和方法制备部分还原氧化石墨烯(pRGO); 由pRGO与核酸适配体 AS1411 及吲哚菁绿(ICG)通过非共价作用构建了光热-光敏纳米复合物 pRGO-AS1411-ICG(pRAI). 利用傅里叶变换红外光谱(FTIR)、拉曼光谱(Raman)、 X射线光电子能谱(XPS)、紫外-可见光谱、透射电子显微镜和 EDS 能谱对 pRGO 和 pRAI 复合物的结构和形貌进行了表征, 并利用细胞实验考察了其肿瘤细胞的光疗-热疗效果. 结果表明, pRAI 以 AS1411 为靶向分子, 可通过光热和光毒性双重作用高效杀伤肿瘤细胞.

关键词: 部分还原氧化石墨烯, 纳米复合材料, 光热疗法, 光动力学疗法, 肿瘤细胞

Abstract:

Partially reduced grphene oxide(pRGO) is synthesized using a mild reduction method by incubating GO suspension under alkaline condition at room tempeature. Aptamer(AS1411) non-covalent binding with cardiogreen(ICG), a photosensitizer and photothermal effect molecule, to the surface of pRGO, was used to target cancer cells for photodynamic therapy(PDT) and photothermal therapy(PTT). Structure and morphology of the as-synthesized pRGO and pRGO-AS1411-ICG(pRAI) nanocomposites were confirmed by menas of FTIR, Raman, XPS, UV-Vis, transmission electron microscopy(TEM) and energy dispersive spectrometer(EDS). pRAI targets cancer cells with AS1411 to produce singlet oxygen for PDT and photothermal effect for PTT upon near-infrared(NIR) light irradiation. Since pRGO is decorated with several AS1411-ICG molecules, the pRGO-AS1411-ICG conjugate yields enhanced binding and therapeutic effect by the added ability to carry multiple photosensitizers. Consequently, pRAI offers a remarkably improved and synergistic therapeutic effect on cells.

Key words: Partially reduced graphene oxide, Nanocomposite, Photothermal therapy, Photodynamic therapy, Tumor cell

中图分类号:

TrendMD:

王雪丽, 王振新. 基于部分还原氧化石墨烯纳米复合材料的肿瘤靶向光动力-光热联合治疗剂的制备. 高等学校化学学报, 2018, 39(10): 2185.

WANG Xueli,WANG Zhenxin. Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide^†. Chem. J. Chinese Universities, 2018, 39(10): 2185.

图/表 7

Scheme 1 Schematic illustration of the synthesis of pRAI

Scheme 2 Schematic presentation of pRAI targeted to HeLa for combined photothermal and photodynamic therapy

Fig.1 UV-Vis absorption spectra of GO(0.02 mg/mL) and pRGO(0.02 mg/mL)(A), TEM images of GO(B1) and pRGO(B2), the curves of pRGO(0.02 mg/mL) in water for 0—14 d(C) and UV-Vis absorption spectra of pRGO(0.02 mg/mL) and pRAI(0.02 mg/mL pRGO)(D)Inset of (A) shows 500—900 nm spectrum and the suspensions of GO(1 mg/mL ) and pRGO(1 mg/mL ); inset of (D) shows UV-Vis absorption spectrum of ICG(40 μmol/L).

Table 1 EDS results of GO and pRGO

Element	Mass(%)		Atomic(%)
Element	GO	pRGO	GO	pRGO
C	61.27	64.09	67.82	71.40
O	38.73	31.95	32.18	26.72
P	—	0.22	—	0.10
S	—	1.60	—	0.67

Fig.2 C1s XPS spectra of GO(A), pRGO(B), full XPS spectra of pRGO and pRAI(C), ATR-FTIR spectra of GO, pRGO and pRAI(D), Raman spectra of GO, pRGO and pRAI(E) and photothermal heating curves of ICG(40 μmol/L), pRGO(200 μg/mL) and pRAI(200 μg/mL), as a function of the irradiation time under continuous laser irradiation at a power intensity of 1.65 W/cm2(F)

Fig.3 Cytotoxicity evaluation test of HeLa cells with different concentrations of pRGO, AS1411, ICG and pRAI(A), calcein AM/PI staining to visualize Hela cell viability treated by pRGO, AS1411, ICG and pRAI(B), cell viability studies with pRGO, AS1411, ICG and pRGO with laser irradiation(808 nm, 1.65 W/cm2 for 10 min)(C) and fluorescence microscope images of cell treated pRGO, AS1411, ICG and pRAI with laser irradiation(808 nm, 1.65 W/cm2 for 10 min)(D)

Fig.4 Cell viability studies with different concentrations of pRAI with and wihout laser irradiation(808 nm,1.65 W/cm2 for 10 min)(A) and fluorescence microscope cell images of SOSG with laser irradiation(808 nm,1.65 W/cm2 for 10 min)(B)

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基于部分还原氧化石墨烯纳米复合材料的肿瘤靶向光动力-光热联合治疗剂的制备

Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide^†

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基于部分还原氧化石墨烯纳米复合材料的肿瘤靶向光动力-光热联合治疗剂的制备

Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide†

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Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide^†