光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤

doi:10.15541/jim20200394

无机材料学报 ›› 2021, Vol. 36 ›› Issue (1): 81-87.DOI: 10.15541/jim20200394

所属专题：【生物材料】肿瘤治疗；【信息功能】Max层状材料、MXene及其他二维材料

光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤

谢雪^1,²,吴建荣²,蔡晓军²,郝俊年²,郑元义^1,²()

^1. 重庆医科大学超声分子影像重点实验室, 重庆400010
^2. 上海交通大学附属第六人民医院, 上海超声医学研究所, 上海 200233

收稿日期:2020-07-14 修回日期:2020-08-13 出版日期:2021-01-20 网络出版日期:2020-08-28
作者简介:谢雪(1992-), 女, 硕士研究生. E-mail: xiexue_moderation@163.com
基金资助:
国家自然科学基金国际合作重点项目(81720108023);国家重点研究发展计划(2018YFC0115200)

Photothermal/pH Responsive B-CuS-DOX Nanodrug for Chemo-photothermal Synergistic Therapy of Tumor

XIE Xue^1,²,WU Jianrong²,CAI Xiaojun²,HAO Junnian²,ZHENG Yuanyi^1,²()

^1. Institute of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing 400010, China
^2. Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, China

Received:2020-07-14 Revised:2020-08-13 Published:2021-01-20 Online:2020-08-28
About author:XIE Xue (1992-), female, Master candidate. E-mail: xiexue_moderation@163.com
Supported by:
The Key Project of International Cooperation and Exchange of NSFC(81720108023);National Key Research and Development Program(2018YFC0115200)

摘要/Abstract

摘要：

基于纳米材料的化疗-光热协同治疗是一种高效的肿瘤治疗方式, 但如何构建具有高载药量与良好光热转换性能的纳米药物依然面临挑战。本研究通过超声剥离法制备二维硼(boron, B)纳米片, 进一步在其表面原位负载超小粒径硫化铜(CuS)纳米颗粒和化疗药阿霉素(DOX), 形成B-CuS-DOX纳米药物。B-CuS具有高的DOX药物装载能力(864 mg/g)和优异的光热转化性能(在808 nm处的光热转换效率为55.8%), 同时可实现pH及近红外激光双重刺激响应而释放药物。细胞实验表明在808 nm近红外光的照射下, B-CuS-DOX展示了良好的化疗-光热协同治疗效果。本研究构建的纳米药物有望为体内肿瘤治疗提供一种有效的化疗-光热协同治疗策略。

关键词: 硼纳米片, 药物递送, 光热治疗, 刺激响应, 肿瘤, 协同治疗

Abstract:

Nanoparticles-based drug delivery system for synergetic chemo-photothermal therapy is an efficient strategy for tumor therapy. However, construction of nanodrugs with high drug loading capacity and good photothermal conversion property is still a great challenge. In this work, two-dimensional boron nanosheets were prepared by ultrasonic liquid exfoliation method, which were further loaded with ultra-small copper sulfide (CuS) nanoparticles and doxorubicin (DOX) to obtain B-CuS-DOX nanocomposites. The prepared B-CuS-DOX exhibited high drug loading capacity (864 mg/g) and excellent photothermal conversion efficiency (55.8%). In addition, B-CuS-DOX exhibited pH and laser--responsive drug release behavior. In vitro results demonstrated that the prepared B-CuS-DOX achieved a good synergistic effect of chemotherapy and photothermal therapy. This work is expected to provide an effective chemo-photothermal synergistic therapy strategy for tumor therapy.

Key words: boron nanosheet, drug delivery, photothermal therapy, stimulus-responsive, tumor, synergistic therapy

中图分类号:

TQ174

谢雪, 吴建荣, 蔡晓军, 郝俊年, 郑元义. 光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤[J]. 无机材料学报, 2021, 36(1): 81-87.

XIE Xue, WU Jianrong, CAI Xiaojun, HAO Junnian, ZHENG Yuanyi. Photothermal/pH Responsive B-CuS-DOX Nanodrug for Chemo-photothermal Synergistic Therapy of Tumor[J]. Journal of Inorganic Materials, 2021, 36(1): 81-87.

图/表 7

图1 B纳米片、B-CuS和B-CuS-DOX的表征

Fig. 1 Characterization of B nanosheets, B-CuS and B-CuS-DOX TEM images of (A) B-CuS and (B) B-CuS; (C) Diameter of B-CuS-DOX; (D) XPS survey spectra of B nanosheets; (E) The selective XPS survey spectra corresponding to B1s spectra; (F) Hydrodynamic size change of B-CuS-DOX dispersed in saline, medium containing fetal bovine serum (FBS), human simulated body fluid (SBF) for 15 d; (G) UV-Vis-NIR spectra and (H) Zeta potential of B nanosheets, B-CuS and B-CuS-DOX; (I) Histogram of the relationship between DOX drug loading and DOX concentration. DOX: doxorubicin

图2 B-CuS的光热转化性能

Fig. 2 Photothermal performance of B-CuS (A) The temperature change of B-CuS dispersion with different concentrations within 5 min of laser irradiation with a power density of 0.5 W/cm2; (B) The temperature change of B-CuS (200 μg/mL) dispersion under different laser power densities for 5 min; (C) Thermal images of B-CuS dispersions with different concentrations after irradiation within 5 min with a laser power density of 0.5 W/cm2; (D) B-CuS photothermal curve under five laser “on-off” cycles; (E) The linear regression equation of the negative natural logarithm of B-CuS heating and cooling time and temperature, θ=ΔT/ΔTmax

图3 B-CuS-DOX在不同pH的PBS溶液及在有无NIR激光照射下的药物释放曲线

Fig. 3 Drug release curves of B-CuS-DOX in PBS solution with different pH and with or without NIR laser irradiation

图4 B-CuS-DOX的细胞摄取行为

Fig. 4 In vitro cellular uptake of B-CuS-DOX (A) CLSM images of 4T1 cells treated with free DOX and B-CuS-DOX with or without laser irradiation; (B) Quantitative analysis of fluorescence intensity of DOX uptake by 4T1 cells in each treatment. Scale bar: 15 μm; *: p < 0.05. DOX: doxorubicin

图5 B-CuS-DOX对细胞的化疗-PTT协同治疗效果评价

Fig. 5 Evaluation of B-CuS-DOX on cell chemotherapy-PTT synergistic therapy (DOX: doxorubicin) (A) Cell survival rate of 4T1 cells incubated with different concentrations of B-CuS for 24 and 48 h; (B) Cell survival rate of 4T1 cells treated with different experimental groups; (C) Therapeutic efficacy of PTT, chemotherapy, chemo-photothermal synergistic therapy and additive therapy. *: p<0.05

图6 4T1细胞存活(calcein-AM染色, 绿色荧光)和死亡(PI双染色, 红色荧光)的荧光显微照片。

Fig. 6 Observation of 4T1 cells stained with calcein AM and PI under confocal microscope (scale: 50 μm). DOX: doxorubicin

图7 流式细胞仪检测4T1细胞经不同治疗方式处理后的细胞凋亡结果

Fig. 7 Detection of apoptosis of 4T1 cells after different treatments by flow cytometry (DOX: doxorubicin)

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光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤

Photothermal/pH Responsive B-CuS-DOX Nanodrug for Chemo-photothermal Synergistic Therapy of Tumor

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