核酸适配子结合无机纳米材料在肿瘤研究中的应用

doi:10.13560/j.cnki.biotech.bull.1985.2017-0301

摘要/Abstract

摘要： 在倡导精准医疗的今日,在基本掌握与肿瘤发生密切相关的靶点的机理后,如何实现肿瘤靶向治疗,尽量消减由治疗带来的不良反应显得尤为关键。核酸适配子是能与靶标以高亲和力、高特异性结合的寡核苷酸;无机纳米材料是纳米材料作为医学领域诊疗制剂中重要的组成部分;利用核酸适配子与靶标结合的特性将其与无机纳米材料结合后,可将靶向结合、生物成像及药物递送等特点集于一体,综合应用于肿瘤研究,同时有力于促进核酸纳米技术的发展。综述了近年不同无机纳米材料结合核酸适配子在肿瘤研究领域中的研究进展,以及对无机纳米材料在医学应用的安全性思考,以期早日实现新型靶向肿瘤治疗策略的开发。

关键词: 核酸适配子, 纳米材料, 肿瘤

Abstract: At nowadays in the promotion of precise medical treatment,how to achieve tumor targeted therapy and reduce the side-effects of radiotherapy is particularly critical after we understood the mechanism of the key molecular targets closely related to tumorigenesis. Aptamers are single-stranded DNA or RNA oligonucleotides which can bind with various targets at high affinity and specificity. Inorganic nanomaterial is an important part of nanomaterial as a medical diagnosis and treatment preparation. Taking the advantage of the properties of aptamers binding with their targets at high affinity,the system of their binding with inorganic nanomaterial can be applied in the tumor research in an integrated approach of targeted binding,biological imaging and drug delivery,concurrently which efficiently promotes the development of nucleic acid nanotechnology. In this review,we discuss the application of varied inorganic nanomaterial binding with the aptamers in tumor research and the safety of inorganic nanomaterial in medical applications,aiming at earlier achieving the development of new targeted therapy strategies to tumor.

Key words: aptamers, nanomaterial, tumor

彭立, 张兴梅. 核酸适配子结合无机纳米材料在肿瘤研究中的应用[J]. 生物技术通报, 2017, 33(11): 48-53.

PENG Li, ZHANG Xing-mei. Application of Aptamers Conjugated Inorganic Nanomaterial in Tumor Research[J]. Biotechnology Bulletin, 2017, 33(11): 48-53.

参考文献

[1] Bao C, Conde J, Curtin J, et al. Bioresponsive antisense DNA gold nanobeacons as a hybrid in vivo theranostics platform for the inhibition of cancer cells and metastasis[J]. Scientific Reports, 2015, 5：12297.
[2] Han H, Valdeperez D, Qiao J, et al. Dual enzymatic reaction-assisted gemcitabine delivery systems for programmed pancreatic cancer therapy[J]. Acs Nano, 2017, 11（2）：1281-1291.
[3] Yang L, Fang Y, Yuan C, et al. Magnetic nanoliposomes as in situ microbubble bombers for multimodality image-guided cancer theranostics[J]. Acs Nano, 2017, 11（2）：1509 -1519.
[4] Zhang Y, Leonard M, et al. Overcoming tamoxifen resistance of human breast cancer by targeted gene silencing using multifunctional pRNA nanoparticles[J]. Acs Nano, 2016, 11（1）：335-346.
[5] Goesmann H, Feldmann C. ChemInform abstract：nanoparticulate functional materials[J]. Cheminform, 2010, 41：1362-1395.
[6] 张中太, 林元华, 唐子龙, 等. 纳米材料及其技术的应用前景[J]. 材料工程, 2000（3）：42-48.
[7] Wang CC, Wu SM, et al. Biomedical applications of DNA-conjugated gold nanoparticles[J]. Chembiochem, 2016, 17：1052-1062.
[8] Kim D, Yong YJ, Jon S. A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer[J]. Acs Nano, 2010, 4（7）：3689-3696.
[9] Chen D, Li B, Cai S, et al. Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy[J]. Biomaterials, 2016, 100：1-16.
[10] Miao X, Li Z, Zhu A, et al. Ultrasensitive electrochemical detection of protein tyrosine kinase-7 by gold nanoparticles and methylene blue assisted signal amplification[J]. Biosensors & Bioelectronics, 2016, 83：39-44.
[11] Arnida, Malugin A, Ghandehari H. Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells：a comparative study of rods and spheres[J]. J Appl Toxicol, 2010, 30（3）：212-217.
[12] Hauck TS, Ghazani AA, Chan WC. Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells[J]. Small, 2008, 4（1）：153-159.
[13] Alkilany AM, Nagaria PK, Hexel CR, et al. Cellular uptake and cytotoxicity of gold nanorods：molecular origin of cytotoxicity and surface effects[J]. Small, 2009, 5（6）：701-708.
[14] Qiu Y, et al. Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods[J]. Biomaterials, 2010, 31：7606-7619.
[15] Wang L, Jiang X, Ji Y, et al. Surface chemistry of gold nanorods：origin of cell membrane damage and cytotoxicity[J]. Nanoscale, 2013, 5（18）：8384-8391.
[16] Yasun E, Li C, Barut I, et al. BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of aptamer-conjugated gold nanorods[J]. Nanoscale, 2015, 7（22）：10240-10248.
[17] Huang YF, Sefah K, Bamrungsap S, et al. Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods[J]. Langmuir, 2008, 24（20）：11860-11865.
[18] Shi H, et al. Au@Ag/Au nanoparticles assembled with activatable aptamer probes as smart “nano-doctors” for image-guided cancer thermotherapy[J]. Nanoscale, 2014, 6（15）：8754-8761.
[19] Qiu L, Chen T, Öçsoy I, et al. A cell-targeted, size-photocontrolla-ble, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy[J]. Nano Letters, 2015, 15（1）：457-463.
[20] 陈功, 殷珺. 磁性纳米材料在生物医学领域的应用[J]. 中国医学装备, 2006, 3（8）：30-32.
[21] Khoshfetrat SM, Mehrgardi MA. Amplified detection of leukemia cancer cells using an aptamer-conjugated gold-coated magnetic nanoparticles on a nitrogen-doped graphene modified electrode[J]. Bioelectrochemistry, 2017, 114：24-32.
[22] Bamrungsap S, Chen T, Shukoor MI, et al. Pattern recognition of cancer cells using aptamer-conjugated magnetic nanoparticles[J]. Acs Nano, 2012, 6（5）：3974-3981.
[23] Sun D, Lu J, Zhong Y, et al. Sensitive electrochemical aptamer cytosensor for highly specific detection of cancer cells based on the hybrid nanoelectrocatalysts and enzyme for signal amplification[J]. Biosens Bioelectron, 2016, 75：301-307.
[24] Zhu H, et al. Aptamer-PEG-modified Fe 3 O 4 @Mn as a novel T1- and T2- dual-model MRI contrast agent targeting hypoxia-induced cancer stem cells[J]. Sci Rep, 2016, 6：39245.
[25] Wei Z, Wu Y, Zhao Y, et al. Multifunctional nanoprobe for cancer cell targeting and simultaneous fluorescence/magnetic resonance imaging[J]. Analytica Chimica Acta, 2016, 938：156-164.
[26] Li J, Wang S, Wu C, et al. Activatable molecular MRI nanoprobe for tumor cell imaging based on gadolinium oxide and iron oxide nanoparticle[J]. Biosens Bioelectron, 2016, 86：1047-1053.
[27] Iijima S. Helical microtubules of graphitic carbon[J]. Nature, 1991, 354（6348）：56-58.
[28] 张金超, 杨康宁, 张海松, 等. 碳纳米材料在生物医学领域的应用现状及展望[J]. 化学进展, 2013, 25（2）：397-408.
[29] Kwon T, Park J, Lee G, et al. Carbon nanotube-patterned surface-based recognition of carcinoembryonic antigens in tumor cells for cancer diagnosis[J]. J Phys Chemi Lett, 2013, 4（7）：1126.
[30] Taghavi S, et al. Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells[J]. Colloids & Surfaces B Biointerfaces, 2015, 140（3）：28-39.
[31] Mohammadi M, Salmasi Z, Hashemi M, et al. Single-walled carbon nanotubes functionalized with aptamer and piperazine-polyethylenimine derivative for targeted siRNA delivery into breast cancer cells[J]. Int J Pharm, 2015, 485（1-2）：50-60.
[32] Tabrizi MA, Shamsipur M. A high sensitive electrochemical aptase-nsor for the determination of VEGF165 in serum of lung cancer patient[J]. Biosens Bioelectron, 2015, 74（12）：764-769.
[33] Kim MG, Shon Y, Lee J, et al. Double stranded aptamer-anchored reduced graphene oxide as target-specific nano detector[J]. Biomaterials, 2014, 35（9）：2999-3004.
[34] 袁丽, 王蓓娣, 等. 介孔二氧化硅纳米粒子应用于可控药物传输系统的若干新进展[J]. 有机化学, 2010（5）：640-647.
[35] Xie X, Li F, Zhang H, et al. EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery[J]. Eur J Pharm Sci, 2016, 83：28-35.
[36] Tang Y, Hu H, Zhang MG, et al. An aptamer-targeting photoresponsive drug delivery system using “off-on” graphene oxide wrapped mesoporous silica nanoparticles[J]. Nanoscale, 2015, 7（14）：6304-6310.
[37] Lam PL, Wong WY, et al. Recent advances in green nanoparticulate systems for drug delivery：efficient delivery and safety concern[J]. Nanomedicine（Lond）, 2017, 12：357-385.
[38] Chompoosor A, et al. The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles[J]. Small, 2010, 6（20）：2246-2249.
[39] Han JW, Jeong JK, Gurunathan S, et al. Male- and female-derived somatic and germ cell-specific toxicity of silver nanoparticles in mouse[J]. Nanotoxicology, 2016, 10（3）：361-373.
[40] Stoccoro A, et al. Multiple endpoints to evaluate pristine and reme-diated titanium dioxide nanoparticles genotoxicity in lung epithelial A549 cells[J], Toxicol Lett, 2017, 276：48-61.
[41] Annangi B, Bach J, et al. Long-term exposures to low doses of cobalt nanoparticles induce cell transformation enhanced by oxidative damage[J]. Nanotoxicology, 2015, 9（2）：138-1347.
[42] Dam DH, et al. Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars[J]. Nanomedicine, 2015, 11：671-679.
[43] Gonzalez L, et al. Co-assessment of cell cycle and micronucleus frequencies demonstrates the influence of serum on the in vitro genotoxic response to amorphous monodisperse silica nanoparticles of varying sizes[J]. Nanotoxicology, 2014, 8：876-884.
[44] Gao N, Bozeman EN, Qian W, et al. Tumor penetrating theranostic nanoparticles for enhancement of targeted and image-guided drug delivery into peritoneal tumors following intraperitoneal delivery[J]. Theranostics, 2017, 7（6）：1689-1704.
[45] Štefančíková L, et al. Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells[J]. J Nanobiotechnology, 2016, 14：63.