药学学报, 2019, 54(6): 1123-1131
引用本文:
张贝贝, 黄维兰, 梅玉影, 邵悦馨, 张璐, 李瑞芳. 智能型荧光纳米递送系统用于乳腺癌细胞的示踪和增殖抑制研究[J]. 药学学报, 2019, 54(6): 1123-1131.
ZHANG Bei-bei, HUANG Wei-lan, MEI Yu-ying, SHAO Yue-xin, ZHANG Lu, LI Rui-fang. Smart fluorescent nano-delivery system for breast cancer cell tracing and growth inhibition[J]. Acta Pharmaceutica Sinica, 2019, 54(6): 1123-1131.

智能型荧光纳米递送系统用于乳腺癌细胞的示踪和增殖抑制研究
张贝贝, 黄维兰, 梅玉影, 邵悦馨, 张璐, 李瑞芳
河南工业大学, 河南 郑州 450001
摘要:
本研究旨在构建一种智能型荧光纳米载体用于肿瘤细胞的示踪,同时通过物理吸附和静电吸附作用,完成模型药物多柔比星(DOX)和小分子干扰RNA(siBcl-2)的负载,实现对肿瘤细胞的协同抑制。本文采用溶胶凝胶法制备介孔硅纳米粒(MSN),共价修饰乙醛化胱氨酸(AC)及聚乙烯亚胺(PEI),所制备的纳米载体MSN-AC-PEI分散均匀,粒径为235.53 nm,电位为14.63 mV;载体材料对siRNA负载比例可达到60:1(质量比),且载体材料可保护siRNA不受RNA酶降解;为模拟肿瘤微环境,DOX在pH 5、10 mmol·L-1谷胱甘肽(GSH)中的释放行为被研究,结果证明,DOX在120 h的累积释放率为正常生理环境的35倍,为其在肿瘤细胞内的智能释放奠定了基础。细胞实验结果表明:MSN-AC-PEI载体材料具有显著的绿色荧光,被肿瘤细胞(MCF-7)摄取后,24 h仍具有示踪能力。纳米递药系统MSN-AC-PEI@DOX/siBcl-2给药24 h后,对肿瘤细胞增殖抑制率可达到40.91%,晚期凋亡率为60.84%。Western blot实验结果表明:与单独DOX及siBcl-2相比,纳米递药系统能显著降低抗凋亡蛋白Bcl-2的表达,从而提升其抗肿瘤能力。
关键词:    荧光      纳米粒      多柔比星      小分子干扰RNA      肿瘤     
Smart fluorescent nano-delivery system for breast cancer cell tracing and growth inhibition
ZHANG Bei-bei, HUANG Wei-lan, MEI Yu-ying, SHAO Yue-xin, ZHANG Lu, LI Rui-fang
Henan University of Technology, Zhengzhou 450001, China
Abstract:
This study aimed to construct an intelligent fluorescent nanocarrier for tumor cell tracing. Doxorubicin (DOX) was used as a model drug, and the gene targeting siBcl-2 was loaded to achieve synergistic inhibition of tumor cells. Mesoporous silicon nanoparticles (MSN) were prepared by a sol-gel method, and acetaldehyde cystine (AC) and polyethyleneimine (PEI) were covalently modified. The prepared nanocarrier MSN-AC-PEI was uniformly dispersed, with a particle size of 235.53 nm and a potential of 14.63 mV. The carrier material MSN-AC-PEI could load siRNA with the mass ratio of 60:1 (Wvectors:WsiRNA) and protect siRNA from RNase I degradation. To simulate the microenvironment of tumor, DOX release in phosphate buffer (pH 5) including 10 mmol·L-1 glutathione (GSH) was investigated. The cumulative release rate of DOX at 120 h is 35 times that of the normal physiological environment, which lays the foundation for the intelligent release of DOX in tumor cells. The results of cell experiments showed that the carrier material MSN-AC-PEI had significant green fluorescence, and the traceability can be maintained for 24 h after taken up by MCF-7 cells. After 24 hours of administration of the nano drug delivery system MSN-AC-PEI@DOX/siBcl-2, the inhibition rate of tumor cell proliferation reached 40.91%, and the late apoptosis rate was 60.84%. The Western blot results showed that compared with free DOX and siBcl-2, the nano-delivery system MSN-AC-PEI@DOX/siBcl-2 can significantly reduce the expression of anti-apoptotic protein Bcl-2, thereby enhancing its anti-tumor ability.
Key words:    fluorescence    nanoparticles    doxorubicin    siRNA    tumor   
收稿日期: 2019-01-23
DOI: 10.16438/j.0513-4870.2019-0074
基金项目: 河南省高等学校重点科研项目计划(17A350005);河南省科技攻关项目资助(182102310245);河南工业大学博士基金项目资助(2015BS012);河南省高校科技创新团队支持计划(19IRTSTHN008).
通讯作者: 张贝贝, 李瑞芳
Email: zhangbb058@163.com;ruifangli2006@yahoo.com
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参考文献:
[1] Zhou Y, Quan G, Wu Q, et al. Mesoporous silica nanoparticles for drug and gene delivery[J]. Acta Pharm Sin B, 2018, 8:165-177.
[2] Baeza A, Colilla M, Vallet-Regi M. Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery[J]. Expert Opin Drug Del, 2015, 12:319-337.
[3] Song Y, Li Y, Xu Q, et al. Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery:advances, challenges, and outlook[J]. Int J Nanomed, 2017, 12:87-110.
[4] Zhong Y, Meng F, Deng C, et al. Ligand-directed active tumor-targeting polymeric nanoparticles for cancer chemotherapy[J]. Biomacromolecules, 2014, 15:1955-1969.
[5] Kobayashi H, Watanabe R, Choyke PL,Improving conventional enhanced permeability and retention (EPR) effects;what is the appropriate target?[J]. Theranostics, 2014, 4:81-89.
[6] Du J, Lane LA, Nie S. Stimuli-responsive nanoparticles for targeting the tumor microenvironment[J]. J Control Release, 2015, 219:205-214.
[7] Semenza GL. The hypoxic tumor microenvironment:a driving force for breast cancer progression[J]. Biochim Biophys Acta, 2016, 1863:382-391.
[8] Liu J, Huang Y, Kumar A, et al. pH-Sensitive nano-systems for drug delivery in cancer therapy[J]. Biotechnol Adv, 2014, 32:693-710.
[9] Quinn JF, Whittaker MR, Davis TP. Glutathione responsive polymers and their application in drug delivery systems[J]. Polym Chem, 2017, 8:97-126.
[10] Wen J, Yang K, Liu F, et al. Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems[J]. Chem Soc Rev, 2017, 46:6024-6045.
[11] Dai Y, Xu C, Sun X, et al. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment[J]. Chem Soc Rev, 2017, 46:3830-3852.
[12] Li R, He Y, Zhang S, et al. Cell membrane-based nanoparticles:a new biomimetic platform for tumor diagnosis and treatment[J]. Acta Pharm Sin B, 2018, 8:14-22.
[13] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68:394-424.
[14] Li X, Kim J, Yoon J, et al. Cancer-associated, stimuli-driven, turn on theranostics for multimodality imaging and therapy[J]. Adv Mater, 2017, 29:1606857.
[15] Abdalla MO, Karna P, Sajja HK, et al. Enhanced noscapine delivery using uPAR-targeted optical-MR imaging trackable nanoparticles for prostate cancer therapy[J]. J Control Release, 2011, 149:314-322.
[16] Garrigue P, Tang J, Ding L, et al. Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors[J]. Proc Natl Acad Sci USA, 2018, 115:11454-11459.
[17] Zhou M, Zhang R, Huang M, et al. A chelator-free multifunctional Cu-64 CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy[J]. J Am Chem Soc, 2010, 132:15351-15358.
[18] Zhong J, Wen L, Yang S, et al. Imaging-guided high-efficient photoacoustic tumor therapy with targeting gold nanorods[J]. Nanomed-Nanotechnol Biol Med, 2015, 11:1499-1509.
[19] Qin H, Zhou T, Yang S, et al. Fluorescence quenching nanoprobes dedicated to in vivo photoacoustic imaging and high-efficient tumor therapy in deep-seated tissue[J]. Small, 2015, 11:2675-2686.
[20] Yang J, Zhang R, Radford DC, et al. FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy[J]. J Control Release, 2015, 218:36-44.
[21] Zhao J, Chen J, Ma S, et al. Recent developments in multimodality fluorescence imaging probes[J]. Acta Pharm Sin B, 2018, 8:320-338.
[22] Du X, Shi B, Tang Y, et al. Label-free dendrimer-like silica nanohybrids for traceable and controlled gene delivery[J]. Biomaterials, 2014, 35:5580-5590.
[23] Hu LL, Meng J, Zhang DD, et al. Functionalization of mesoporous organosilica nanocarrier for pH/glutathione dual-responsive drug delivery and imaging of cancer therapy process[J]. Talanta, 2018, 177:203-211.
[24] Yang B, Chen Y, Shi J. Exogenous/endogenous-triggered mesoporous silica cancer nanomedicine[J]. Adv Healthc Mater, 2018, 7:1800268.
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