药学学报, 2019, 54(8): 1502-1508
引用本文:
王亚婷, 张振华, 冯倩华, 蔺萌. 基于中空介孔硫化铜的多功能纳米递药系统的构建及初步研究[J]. 药学学报, 2019, 54(8): 1502-1508.
WANG Ya-ting, ZHANG Zhen-hua, FENG Qian-hua, LIN Meng. Construction and preliminary study of multifunctional drug delivery system based on hollow mesoporous copper sulfide nanoparticles[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1502-1508.

基于中空介孔硫化铜的多功能纳米递药系统的构建及初步研究
王亚婷1, 张振华1, 冯倩华2, 蔺萌1
1. 郑州大学基础医学院, 河南 郑州 450001;
2. 郑州大学药学院, 河南 郑州 450001
摘要:
本文拟构建一种基于中空介孔硫化铜(hollow mesoporous copper sulfide nanoparticles,HMCuS)纳米粒的多功能纳米递药系统,以实现肿瘤靶向的光动力学治疗与化疗的协同治疗。本文采用置换法合成HMCuS纳米粒载体,负载多柔比星(doxorubicin,DOX)抗癌药物后由透明质酸(hyaluronic acid,HA)进行表面修饰,从而制备DOX/HMCuS-HA抗癌药物系统。结果表明:所制备的DOX/HMCuS-HA呈现均匀球状结构,载药量为33.6%,粒径和电位分别为113.8±6.9 nm和18.4±2.8 mV。100μg·mL-1 HMCuS在808 nm激光(2 W·cm-2)下照射8 min可升温51℃,具有较好的产热效果。此外,电子自旋共振(electron spin resonance,ESR)及亚甲基蓝(methylene blue,MB)实验结果表明,HMCuS在近红外光(near infrared,NIR)照射下同时可以产生羟自由基(·OH)介导光动力学治疗。体外释药结果表明,制剂需经透明质酸酶降解后,在酸性pH值和NIR触发下促进DOX的释放,实现靶向多刺激响应型门控释药。以上结果为及时有效的抗肿瘤治疗提供了新的策略。
关键词:    纳米粒      硫化铜      靶向      光动力学治疗      光热治疗     
Construction and preliminary study of multifunctional drug delivery system based on hollow mesoporous copper sulfide nanoparticles
WANG Ya-ting1, ZHANG Zhen-hua1, FENG Qian-hua2, LIN Meng1
1. School of Basic Medical Sciences, Zhengzhou University, Zhenzhou 450001, China;
2. School of Pharmaceutical Sciences, Zhengzhou University, Zhenzhou 450001, China
Abstract:
This study aims to develop multifunctional drug delivery system based on hollow mesoporous copper sulfide (HMCuS) nanoparticles. This type of nanoparticles is expected to achieve the synergistic treatment of tumor by targeted phototherapy and chemotherapy. The carrier was synthesized by a substitution method, and the anti-cancer drug doxorubicin (DOX) was loaded and then modified by hyaluronic acid (HA) to prepare the anticancer drug system DOX/HMCuS-HA. The results suggested that DOX/HMCuS-HA presented uniform spherical structure, with the drug loading efficiency of 33.6%, the particle size and zeta potential being 113.8±6.9 nm and 18.4±2.8 mV, respectively. When 100 μg·mL-1 HMCuS was irradiated under 808 nm laser (2 W·cm-2) for 8 min, the temperature can heat up 51℃, demonstrating high photothermal conversion efficacy. Electron spin resonance (ESR) tests and methylene blue degradation experiments showed that HMCuS nanoparticles could simultaneously produce hydroxyl radical (·OH) mediated photodynamic therapy. In addition, HA was responsible for minimizing premature drug release and increasing tumor targeting efficiency by acting as a smart gatekeeper with tumor specific targeting moiety. In vitro drug release experiments showed that the coated HA could be degraded by intracellular lysosomal enzyme hyaluronidase, which facilitated DOX release. The acidic microenvironment of tumor cell and external near infrared (NIR) stimulus could trigger further release of DOX from the nanoparticles. These results point to a new strategy for timely and effective anti-tumor treatment.
Key words:    nanoparticle    copper sulfide    targeting    photodynamic therapy    photothermal therapy   
收稿日期: 2019-04-08
DOI: 10.16438/j.0513-4870.2019-0253
基金项目: 国家自然科学基金资助项目(81202485,81273451).
通讯作者: 蔺萌,Tel:86-371-67781959,E-mail:linmeng0202@126.com
Email: linmeng0202@126.com
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参考文献:
[1] Chen WQ. Cancer statistics:updated cancer burden in China[J]. Chin J Cancer Res, 2015, 27:1
[2] Overchuk M, Zheng G. Overcoming obstacles in the tumor microenvironment:recent advancements in nanoparticle delivery for cancer theranostics[J]. Biomaterials, 2018, 156:217-237.
[3] Awasthi R, Roseblade A, Hansbro PM, et al. Nanoparticles in cancer treatment:opportunities and obstacles[J]. Curr Drug Targets, 2018, 19:1696-1709.
[4] Wang JL, Kaplan JA, Colson YL, et al. Mechanoresponsive materials for drug delivery:harnessing forces for controlled release[J]. Adv Drug Deliv Rev, 2017, 108:68-82.
[5] Pan QB, Zhang J, Li X, et al. Preparation and in vitro evaluation of phospholipid-coated silver-graphene quantum dot multifunctional nanoparticles[J]. Acta Pharm Sin (药学学报), 2019, 54:366-372.
[6] Dissanayake S, Denny WA, Gamage S, et al. Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides[J]. J Control Release, 2017, 250:62-76.
[7] Zong L, Yuan AR, Zhu Y, et al. Preparation of thermoresponsive micelles loaded with indocyanine green and doxorubicin for combined therapy in MCF-7 cells[J]. Acta Pharm Sin (药学学报), 2018, 53:1169-1176.
[8] Miao YQ, He SF, Liang JY, et al. Preliminary study of lipid bilayer-coated calcium phosphate nanoparticles as a drug carrier for antitumor drug[J]. Acta Pharm Sin (药学学报), 2017, 52:977-984.
[9] Bu XY, Zhou D, Li J, et al. Copper sulfide self-assembly architectures with improved photothermal performance[J]. Langmuir, 2014, 30:1416-1423.
[10] Guo LR, Yan DD, Yang DF, et al. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles[J]. ACS Nano, 2014, 8:5670-5681.
[11] Dong K, Liu Z, Li ZH, et al. Hydrophobic anticancer drug delivery by a 980 nm laser-driven photothermal vehicle for efficient synergistic therapy of cancer cells in vivo[J]. Adv Mater, 2013, 25:4452-4458.
[12] Bai J, Liu YW, Jiang XE. Multifunctional PEG-GO/CuS nanocomposites for near-infrared chemo-photothermal therapy[J]. Biomaterials, 2014, 35:5805-5813.
[13] Wang SH, Riedinger A, Li HB, et al. Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects[J]. ACS Nano, 2015, 9:1788-1800.
[14] Shi H, Sun YD, Yan RQ, et al. Magnetic semiconductor Gddoping CuS nanoparticles as activatable nanoprobes for bimodal imaging and targeted photothermal therapy of gastric tumors[J]. Nano Lett, 2019, 19:937-947.
[15] Tian QW, Hu JQ, Zhu YH, et al. Sub-10 nm Fe3O4@Cu2-xS core-shell nanoparticles for dual-modal imaging and photothermal therapy[J]. J Am Chem Soc, 2013, 135:8571-8577.
[16] Qiu LP, Long MM, Chen DW. Hyaluronic acid-based carriers for tumor targeted delivery system[J]. Acta Pharm Sin (药学学报), 2013, 48:1376-1382.
[17] Choi KY, Saravanakumar G, Park JH, et al. Hyaluronic acidbased nanocarriers for intracellular targeting:interfacial interactions with proteins in cancer[J]. Colloids Sur B, 2012, 99:82-94.
[18] Hou L, Zhang HJ, Wang YT, et al. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent[J]. Int J Nanomed, 2015, 10:4507-4520.
[19] Hou L, Feng QH, Wang YT, et al. Multifunctional nanosheets based on hyaluronic acid modified graphene oxide for tumortargeting chemophotothermal therapy[J]. J Nanopart Res, 2015, 17:162.
[20] Jia L, Qiao MX, Hu HY, et al. The characterisitics of temperature/pH sensitive block copolymer micelles in vitro[J]. Acta Pharm Sin (药学学报), 2011, 46:839-844.
[21] Wang ZZ, Chen ZW, Liu Z, et al. A multi-stimuli responsive gold nanocage-hyaluronic platform for targeted photothermal and chemotherapy[J]. Biomaterials, 2014, 35:9678-9688.
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