介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

doi:10.15541/jim20200091

无机材料学报 ›› 2020, Vol. 35 ›› Issue (12): 1365-1372.DOI: 10.15541/jim20200091 CSTR: 32189.14.10.15541/jim20200091

所属专题：生物材料论文精选(2020)； 2019~2020年度优秀作者作品欣赏(六)

介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

曾雨淋^1,²(),陈佳杰^1,³,田正芳²,朱敏¹(),朱钰方^2,³()

1. 上海理工大学材料科学与工程学院, 上海 200093
2. 黄冈师范学院化学化工学院, 催化材料制备及应用湖北省重点实验室, 黄冈 438000
3. 中国科学院上海硅酸盐研究所, 上海 200050

收稿日期:2020-02-24 修回日期:2020-03-10 出版日期:2020-12-20 网络出版日期:2020-04-05
作者简介:曾雨淋(1995–), 女, 硕士研究生. E-mail: 1591422585@qq.com
基金资助:
国家自然科学基金面上项目(51572172);上海理工大学科技发展项目(2018KJFZ016);上海理工大学科技发展项目(2019KJFZ023)

Preparation of Mesoporous Organosilica-based Nanosystem for in vitro Synergistic Chemo- and Photothermal Therapy

ZENG Yulin^1,²(),CHEN Jiajie^1,³,TIAN Zhengfang²,ZHU Min¹(),ZHU Yufang^2,³()

1. School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
2. Hubei Key Laboratory of Processing and Application of Catalytic Materials, College of Chemical Engineering, Huanggang Normal University, Huanggang 438000, China
3. Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China

Received:2020-02-24 Revised:2020-03-10 Published:2020-12-20 Online:2020-04-05
About author:ZENG Yulin (1995–), female, Master candidate. E-mail: 1591422585@qq.com
Supported by:
National Natural Science Foundation of China(51572172);University of Shanghai for Science and Technology(2018KJFZ016);University of Shanghai for Science and Technology(2019KJFZ023)

摘要/Abstract

摘要：

有机/无机杂化的介孔有机硅纳米颗粒因其高的比表面积、丰富的介孔孔道、功能性的骨架以及高的药物装载量等特点而在生物医学领域受到广泛关注。本研究提出以二硫键桥接的有机/无机杂化介孔有机硅纳米颗粒为载体共装载化疗药物和光热剂, 设计制备以DNA分子作为控释“开关”修饰介孔有机硅纳米颗粒的纳米递送系统(ICG/DOX-MONs @DNA₂₀)。该纳米递送系统结合了光热剂的光热效应以及DNA分子随温度升高而从颗粒表面脱附的特性, 可实现近红外光照射激发药物在肿瘤细胞中的控制释放, 同时获得药物化疗-光热联合治疗肿瘤的效果。实验结果表明, 纳米递送系统在近红外光照下能迅速升温至43 ℃以上的热疗温度, 而且在37 ℃条件下6 h内仅缓慢释放药物12.3%, 而当温度升至43 ℃时则快速释放药物52.4%; 细胞实验显示该纳米递送系统能够被HeLa肿瘤细胞吞噬, 在近红外光照下有明显的药物化疗-光热联合治疗效果。因此, ICG/DOX-MONs@DNA₂₀纳米递送系统在药物化疗-光热联合治疗肿瘤方面具有应用前景。

关键词: 介孔有机硅, 纳米载体, 控制释放, 联合治疗

Abstract:

Organic-inorganic hybrid mesoporous organosilica has gained more attention in biomedicine due to its high surface area, mesoporous channels, functional framework, and high drug loading capacity. In this study, disulfide- bridged hybrid mesoporous organosilica nanoparticles (MONs) as nanocarriers were employed to construct a nanosystem (ICG/DOX-MONs@DNA₂₀) for delivering drugs and photothermal agents, in which DNA molecules as “switches” were modified on the surface of MONs to control drug release. The results showed that the ICG/DOX-MONs@DNA₂₀ nanosystem could increase the temperature to above 43 ℃ for photothermal therapy with near-infrared (NIR) laser irradiation. On the other hand, the ICG/DOX-MONs@DNA₂₀ nanosystem exhibited a very slow release of DOX (12.3% in 6 h) at 37 ℃, but a rapid release of DOX (52.4% in 6 h) occurred at 43 ℃. Cell culture experiments indicated that the nanosystem can be internalized by HeLa cells, and exhibited an enhanced therapeutic efficacy of synergistic chemo- and photothermal therapy. Hence, the ICG/DOX-MONs@DNA₂₀ nanosystem might be promising for synergistic chemo- and photo-thermal tumor therapy.

Key words: mesoporous organosilica, nanocarriers, controlled release, synergistic therapy

中图分类号:

TQ174

曾雨淋, 陈佳杰, 田正芳, 朱敏, 朱钰方. 介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究[J]. 无机材料学报, 2020, 35(12): 1365-1372.

ZENG Yulin, CHEN Jiajie, TIAN Zhengfang, ZHU Min, ZHU Yufang. Preparation of Mesoporous Organosilica-based Nanosystem for in vitro Synergistic Chemo- and Photothermal Therapy[J]. Journal of Inorganic Materials, 2020, 35(12): 1365-1372.

图/表 7

图1 MONs的形貌、结构表征

Fig. 1 Characterization of MONs (a) SEM image of MONs; (b) TEM images of MONs; (c) DLS particle size distribution of MONs; (d) N2 adsorption-desorption isotherm and the corresponding pore size distribution of MONs

图2 MONs、MONs-NH2、ICG/DOX-MONs和ICG/DOX-MONs@DNA20纳米颗粒的(a)Zeta表面电位变化, (b)FT-IR谱图, 及(c)UV-Vis光谱图

Fig. 2 (a) Zeta potential, (b) FT-IR spectra and (c) UV-Vis spectra of MONs, MONs-NH2, ICG/DOX-MONs and ICG/DOX-MONs@DNA20 nanoparticles

图3 (a)不同浓度ICG/DOX-MONs@DNA20悬浮液在0.75 W/cm2的近红外光照射下的光热升温曲线与(b) 100 μg/mL的ICG/DOX-MONs@DNA20悬浮液在不同功率密度的近红外光照射下的光热升温曲线

Fig. 3 Photothermal heating curves of ICG/DOX- MONs@DNA20 suspension with different concentrations under NIR irradiation at 0.75 W/cm2, and (b) photothermal heating curves of 100 μg/mL ICG/DOX-MONs@DNA20 suspension under NIR irradiation at different power densities

图4 ICG/DOX-MONs@DNA20在37和43 ℃条件下的(a) DOX和(b) ICG的释放曲线, 以及(c) ICG/DOX-MONs@DNA20在37和43 ℃交替变温条件下的DOX和ICG的释放曲线

Fig. 4 Release profiles of (a) DOX and (b) ICG from ICG/DOX-MONs@DNA20 at 37 and 43 ℃, respectively, and (c) release profile of DOX and ICG from ICG/DOX-MONs@DNA20 at the alternating temperature between 37 and 43 ℃

图5 MONs对HeLa细胞与不同浓度MONs共培养24和48 h后的细胞活性情况

Fig. 5 Cell viability of HeLa cells cultured with MONs with different concentrations for 24 and 48 h

图6 HeLa细胞与不同颗粒共培养3 h后的细胞吞噬不同颗粒结果(蓝色: 细胞核; 红色: DOX)

Fig. 6 Cell uptake of different nanoparticles after being cultured with HeLa cells for 3 h (blue: nuclei; red: DOX)

图7 HeLa细胞与ICG/DOX-MONs和ICG/DOX-MONs@DNA20共培养后在有或无近红外光照下的细胞存活率

Fig. 7 Cell viabilities of HeLa cells cultured with ICG/DOX-MONs and ICG/DOX-MONs@DNA20 with or without NIR irradiation *P<0.05, ***P<0.001

参考文献 29

[1]	WEN JIA, YANG KUI, LIU FENG-YU, et al. Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Wiley Interdisciplinary Reviews, 2017,46(19):6024-6045.
[2]	ZHANG YA-RU, LIN RUN, LI HONG-JUN, et al. Strategies to improve tumor penetration of nano-medicines through nanoparticle design. Wiley Interdisciplinary Reviews, 2019,11(1):e1519-1-12. DOI URL PMID
[3]	QIAO YI-TIAN, WAN JIAN-QIN, ZHOU LI-QIAN, et al. Stimuli- responsive nanotherapeutics for precision drug delivery and cancer therapy. Wiley Interdisciplinary Reviews, 2019,11(1):e1527-1-20. DOI URL PMID
[4]	OVERCHUK MARTA, ZHENG GANG. Overcoming obstacles in the tumor microenvironment: recent advancements in nanoparticle delivery for cancer theranostics. Biomaterials, 2018,156:217-237. DOI URL PMID
[5]	VANKAYALA RAVIRAJ, HWANG KUO-CHU. Near-infrared-light- activatable nanomaterial mediated phototheranostic nanomedicines: an emerging paradigm for cancer treatment. Advanced Materials, 2018,30(23):1706320-1-7. DOI URL
[6]	HAYASHI KOICHIRO, MARUHASHI TAKUMA. One-pot synthesis of dual stimulus-responsive degradable hollow hybrid nanoparticles for imageguided trimodal therapy. Advanced Functional Materials, 2016,26(47):8613-8622. DOI URL
[7]	WANG ZHENG, ZHANG FAN, SHAO DAN, et al. Janus nanobullets combine photodynamic therapy and magnetic hyperthermia to potentiate synergetic anti-metastatic immunotherapy. Advanced Science, 2019,6(22):1901690-1-10. DOI URL PMID
[8]	FAN WEN-PEI, LU NAN, HUANG PING. Glucose-responsive sequential generation of hydrogen peroxide and nitric oxide for synergistic cancer starving-like/gas therapy. Angewandte Chemie International Edition, 2017,56(5):1229-1233. DOI URL PMID
[9]	FAN WEN-PEI, LU NAN, SHEN ZHE-YU. Generic synthesis of small-sized hollow mesoporous organo-silica nanoparticles for oxygen-independent X-ray-activated synergistic therapy. Nature Communications, 2019,10(1):1-14. DOI URL PMID
[10]	WU JIAN-RONG, BREMNER DAVID H, NIU SHI-WEI, et al. Chemodrug-gated biodegradable hollow mesoporous organosilica nanotheranostics for multi-modal imaging-guided low-temperature photo-thermal therapy/chemotherapy of cancer. ACS Applied Materials & Interfaces, 2018,10(49):42115-42126. DOI URL PMID
[11]	LI ZHEN-LI, HAN JUN, YU LUO-DAN, et al. Synergistic sonodynamic/chemotherapeutic suppression of hepatocellular carcinoma by targeted biodegradable mesoporous nanosonosensitizers. Advanced Functional Materials, 2018,28(26):1800 145-1-16.
[12]	LI LING, YANG ZHEN, FAN WEN-PEI, et al. In situ polymerized hollow mesoporous organosilica bio-catalysis nanoreactor for enhancing ROS-mediated anticancer therapy. Advanced Functional Materials, 2020,30(4):1907716-1-11. DOI URL PMID
[13]	CHEN JIA-JIE, LIU JIA-XING, HU YA-PING, et al. Metal-organic framework-coated magnetite nano-particles for synergistic magnetic hyperthermia and chemotherapy with pH-triggered drug release. Science and Technology of Advanced Materials, 2019,20(1):1043-1054. DOI URL PMID
[14]	FAN WEN-PEI, YUNG BRYANT, HUANG PING. Nanotechnology for multimodal synergistic cancer therapy. Chemical Reviews, 2017,117(22):13566-13638. DOI URL PMID
[15]	PRASAD MINAKSHI, LAMBE UPENDRA P, et al. Nanotherapeutics: an insight into healthcare and multi-dimensional applications in medical sector of the modern world. Biomedicine & Pharmacotherapy, 2018,97:1521-1537. DOI URL PMID
[16]	KOTARO MATSUMOTO, TAN LE HOANG DOAN, NGOC XUAN DAT MAI, et al. Anticancer drug delivery capability of biodegradable PMO in the chicken egg tumor model. Enzymes, 2018,44:103-116. URL PMID
[17]	AGRAWAL GARIMA, AGRAWAL RAHUL. Janus nanoparticles: recent advances in their interfacial and biomedical applications. ACS Applied Nano Materials, 2019,2(4):1738-1757.
[18]	MA BAO-YUAN, TIAN ZHENG-FANG, ZHU YU-FANG. Biodegradable silicon-based mesoporous nanoparticles for nanomedicine. Journal of Bio-analysis & Biomedicine, 2018,10(6):e159.
[19]	TANG WEI, FAN WEN-PEI, WANG ZHAN-TONG. Acidity/ reducibility dual-responsive hollow mesoporous organosilica nanoplatforms for tumor-specific self-assembly and synergistic therapy. ACS Nano, 2018,12(12):12269-12283. DOI URL PMID
[20]	HUANG PING, CHEN YU, HAN LIN, et al. Molecularly organic/ inorganic hybrid hollow mesop-orous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality. Biomaterials, 2017,125:23-37. DOI URL PMID
[21]	YU LUO-DAN, CHEN YU, LIN HAN, et al. Ultra-small mesoporous organosilica nanoparticles: morphology modulations and redox-responsive bio-degradability for tumor-specific drug delivery. Biomaterials, 2018,161:292-305. DOI URL PMID
[22]	JONAS G CROISSANT, YEVHEN FATIEIEV, ABDULAZIZ ALMALIK, et al. Mesoporous silica and organosilica nanoparticles: physical chemistry, biosafety, delivery strategies, and biomedical applications. Advanced Healthcare Materials, 2018,7(4):1700831-1-75. DOI URL
[23]	FENTON OWEN S, OLAFSON KATY N, PILLAI PADMINI S, et al. Advances in biomaterials for drug delivery. Advanced Materials, 2018,30(29):1705328-1-29.
[24]	XU YI, ZHU YU-FANG, KASKEL STEFAN. A smart magnetic nanosystem with controllable drug release and hyperthermia for potential cancer therapy. RSC Advances, 2015,5(121):99875-99883.
[25]	HUANG PING, QIAN XIAO-QIN, CHEN YU, et al. Metalloporphyrin-encapsulated biodegradable nano-systems for highly efficient magnetic resonance imaging-guided sonodynamic cancer therapy. Journal of the American Chemical Society, 2017,139(3):1275-1284. URL PMID
[26]	TAO CUI-LIAN, ZHU YU-FANG, XU YI, ZHU MIN, et al. Mesoporous silica nanoparticles for enhancing the delivery efficiency of immuno-stimulatory DNA drugs. Dalton Trans, 2014,43(13):5142-1-50. DOI URL PMID
[27]	LAI XIN, SUN DAN, HOU YI, et al. Amino- functionalized multilayer core-shell mesoporous organo-silica nanospheres for Cr(VI) removal. Advanced Materials Interfaces, 2018,5(18):1800630-1-11.
[28]	HU LIN-LIN, MENG JIE, ZHANG DAN-DAN, et al. Functionalization of mesoporous organosilica nano-carrier for pH/glutathione dual-responsive drug delivery and imaging of cancer therapy process. Talanta, 2018,177:203-211. DOI URL PMID
[29]	DOUSTKHAH ESMAIL, MOHTASHAM HAMED, FARAJZADEH MUSTAFA, et al. Organosiloxane tunability in mesoporous organosilica and punctuated Pd nanoparticles growth; theory and experiment. Microporous and Mesoporous Materials, 2020,293:109832-1-8. DOI URL

介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

Preparation of Mesoporous Organosilica-based Nanosystem for in vitro Synergistic Chemo- and Photothermal Therapy

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 7

参考文献 29

相关文章 5

编辑推荐

Metrics

本文评价

[1]	白志强, 赵璐, 白云峰, 冯锋. MXenes的制备、性质及其在肿瘤诊疗中的研究进展[J]. 无机材料学报, 2022, 37(4): 361-375.
[2]	张文君, 赵雪莹, 吕江维, 曲有鹏. 中空有序介孔有机硅的研究进展: 制备及在肿瘤治疗中的应用[J]. 无机材料学报, 2022, 37(11): 1192-1202.
[3]	王玉伟, 陈佳杰, 田正芳, 朱敏, 朱钰方. 卟啉基金属有机框架负载高铁酸钾: 光-化学动力学联合治疗肿瘤性能研究[J]. 无机材料学报, 2021, 36(12): 1305-1315.
[4]	杨劢, 朱敏, 陈雨, 朱钰方. FePS₃纳米片制备及其体外光热-光动力学联合治疗性能研究[J]. 无机材料学报, 2021, 36(10): 1074-1082.
[5]	王彦卿,张朝平. 诺氟沙星明胶磁性微球的研制及表征[J]. 无机材料学报, 2005, 20(1): 77-82.