三维肿瘤细胞模型在纳米载体性能评价中的应用

doi:10.3969/j.issn.0258-8021.2023.01.011

Abstract
Figure/Table
References
Related Citation (7)

Download: PDF (2466 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Nanocarriers may selectively accumulate in tumor tissues through enhanced permeability and retention effect (EPR) or actively targeting functions, and thereby improve the therapeutic efficacy. A range of physicochemical parameters including the size, shape, surface charge, and ligands attachment have been found influencing penetration of nanocarriers in the tumor tissue. Compared with two-dimensional (2D) monolayer cell cultures, three-dimensional (3D) tumor spheroids can better mimic the characteristics of the natural tumor tissues, and therefore have been widely used in the evaluation of tumor penetration and therapeutic efficacy of nanocarriers in recent years. In this review, we will introduce the properties and the preparation methods of 3D tumor spheroids, summarize recent studies investigating the interaction between nanoparticles and 3D tumor spheroids, and discuss the factors that affect the penetration behaviors, therapeutic effects and the intrinsic toxicity of nanocarriers.

Key words： 3D tumor spheroid nanocarrier enhanced permeability and retention(EPR) effect targeting penetration

Received: 29 September 2021

PACS:

R318

Corresponding Authors: ^*E-mail: yuyingzhang@nankai.edu.cn

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Yu Chongli
	Zhang Yuying

Cite this article:

Yu Chongli,Zhang Yuying. Application of 3D Tumor Spheroids in Evaluation of Nanocarriers[J]. Chinese Journal of Biomedical Engineering, 2023, 42(1): 99-109.

URL:

http://cjbme.csbme.org/EN/10.3969/j.issn.0258-8021.2023.01.011 OR http://cjbme.csbme.org/EN/Y2023/V42/I1/99

[1] Chaturvedi VK, Singh A, Singh VK, et al. Cancer nanotechnology: a new revolution for cancer diagnosis and therapy [J]. Curr Drug Metab, 2019, 20(6): 416-429.
[2] Roma-Rodrigues C, Mendes R, Baptista PV, et al. Targeting tumor microenvironment for cancer therapy [J]. Int J Mol Sci, 2019, 20(4): 840.
[3] Roma-Rodrigues C, Pombo I, Raposo L, et al. Nanotheranostics targeting the tumor microenvironment [J]. Front Bioeng Biotechnol, 2019, 7: 197.
[4] Saglam-Metiner P, Gulce-Iz S, Biray-Avci C Bioengineering-inspired three-dimensional culture systems: Organoids to create tumor microenvironment [J]. Gene, 2019, 686: 203-212.
[5] Souza AG, Silva IBB, Campos-Fernandez E, et al. Comparative assay of 2D and 3D cell culture models: proliferation, gene expression and anticancer drug response [J]. Curr Pharm Des, 2018, 24(15): 1689-1694.
[6] Gao Yue, Li Mingguang, Chen Bin, et al. Predictive models of diffusive nanoparticle transport in 3-dimensional tumor cell spheroids [J]. AAPS J, 2013, 15(3): 816-831.
[7] 郭雷雷, 徐郁蕊, 张蕾,等. 三维肿瘤球模型应用于肿瘤耐药机制研究进展 [J]. 中国药科大学学报, 2018, 49(5): 521-527.
[8] Bai Chujie, Yang Min, Fan Zhengfu, et al. Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma [J]. J Exp Clin Cancer Res, 2015, 34(1): 58.
[9] Melissaridou S, Wiechec E, Magan M, et al. The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer [J]. Cancer Cell Int, 2019, 19: 16.
[10] 代献花, 张廷英, 黄勇, 等. 基于纳米载体的抗肿瘤药物研究进展 [J]. 肿瘤药学, 2019, 9(6): 850-854.
[11] Roma-Rodrigues C, Pombo I, Fernandes AR, et al. Hyperthermia induced by gold nanoparticles and visible light photothermy combined with chemotherapy to tackle doxorubicin sensitive and resistant colorectal tumor 3D spheroids [J]. Int J Mol Sci, 2020, 21(21): 8017.
[12] Bell HS, Whittle IR, Walker M, et al. The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems [J]. Neuropathol Appl Neurobiol, 2001, 27(4): 291-304.
[13] Kamatar A, Gunay G, Acar H Natural and synthetic biomaterials for engineering multicellular tumor spheroids [J]. Polymers (Basel), 2020, 12(11): 2506.
[14] Calpe B, Kovacs WJ High-throughput screening in multicellular spheroids for target discovery in the tumor microenvironment [J]. Expert Opin Drug Discov, 2020, 15(8): 955-967.
[15] Kim SJ, Kim EM, Yamamoto M, et al. Engineering multi-cellular spheroids for tissue engineering and regenerative medicine [J]. Adv Healthc Mater, 2020, 9: e2000608.
[16] Lu Hongxu, Hoshiba T, Kawazoe N, et al. Cultured cell-derived extracellular matrix scaffolds for tissue engineering [J]. Biomaterials, 2011, 32(36): 9658-9666.
[17] 卓志远, 陈刚, 刘华, 三维细胞培养技术的进展及其在肿瘤研究中的应用 [J]. 肿瘤, 2018, 38(5): 502-507.
[18] Friedrich J, Seidel C, Ebner R, et al. Spheroid-based drug screen: considerations and practical approach [J]. Nat Protoc, 2009, 4(3): 309-324.
[19] Foty R, A simple hanging drop cell culture protocol for generation of 3D spheroids [J]. J Vis Exp, 2011(51): 2720.
[20] Ware MJ, Colbert K, Keshishian V, et al. Generation of homogenous three-dimensional pancreatic cancer cell spheroids using an improved hanging drop technique [J]. Tissue Eng Part C Methods, 2016, 22(4): 312-321.
[21] Sabhachandani P, Motwani V, Cohen N, et al. Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform [J]. Lab Chip, 2016, 16(3): 497-505.
[22] Fang Guocheng, Lu Hongxu, Law A, et al. Gradient-sized control of tumor spheroids on a single chip [J]. Lab Chip, 2019, 19(24): 4093-4103.
[23] Krishnan MA, Yadav K, Chelvam V Agarose micro-well platform for rapid generation of homogenous 3D tumor spheroids [J]. Curr Protoc, 2021, 1(7): e199.
[24] Sontheimer-Phelps A, Hassell BA, Ingber DE Modelling cancer in microfluidic human organs-on-chips [J]. Nat Rev Cancer, 2019, 19(2): 65-81.
[25] Sun Wujin, Luo Zhimin, Lee J, et al. Organ-on-a-Chip for cancer and immune organs modeling [J]. Adv Healthc Mater, 2019, 8(4): e1801363.
[26] Shield K, Ackland ML, Ahmed N, et al. Multicellular spheroids in ovarian cancer metastases: biology and pathology [J]. Gynecol Oncol, 2009, 113(1): 143-148.
[27] Dadwal A, Baldi A, Kumar Narang R Nanoparticles as carriers for drug delivery in cancer [J]. Artif Cells Nanomed Biotechnol, 2018, 46(sup2): 295-305.
[28] Kunz-Schughart LA, Freyer JP, Hofstaedter F, et al. The use of 3-D cultures for high-throughput screening: the multicellular spheroid model [J]. J Biomol Screen, 2004, 9(4): 273-285.
[29] Salatin S, Dizaj SM, Khosroushahi AY Effect of the surface modification, size, and shape on cellular uptake of nanoparticles [J]. Cell Biol Int, 2015, 39(8): 881-890.
[30] Durymanov M, Kroll C, Permyakova A, et al. Role of endocytosis in nanoparticle penetration of 3D pancreatic cancer spheroids [J]. Mol Pharm, 2019, 16(3): 1074-1082.
[31] Zhou Mengxue, Huang Hui, Wang Dongqing, et al. Light-triggered PEGylation/ dePEGylation of the nanocarriers for enhanced tumor penetration [J]. Nano Lett, 2019, 19(6): 3671-3675.
[32] Lazzari G, Vinciguerra D, Balasso A, et al. Light sheet fluorescence microscopy versus confocal microscopy: in quest of a suitable tool to assess drug and nanomedicine penetration into multicellular tumor spheroids [J]. Eur J Pharm Biopharm, 2019, 142: 195-203.
[33] Niora M, Pedersbaek D, Munter R, et al. Head-to-head comparison of the penetration efficiency of lipid-based nanoparticles into tumor spheroids [J]. ACS Omega, 2020, 5(33): 21162-21171.
[34] Huang Keyang, Ma Huili, Liu Juan, et al. Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo [J]. ACS Nano, 2012, 6(5): 4483-4493.
[35] Sujai PT, Joseph MM, Saranya G, et al. Surface charge modulates the internalization vs. penetration of gold nanoparticles: comprehensive scrutiny on monolayer cancer cells, multicellular spheroids and solid tumors by SERS modality [J]. Nanoscale, 2020, 12(13): 6971-6975.
[36] Wicki A, Witzigmann D, Balasubramanian V, et al. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications [J]. J Control Release, 2015, 200: 138-157.
[37] Chen Hongmin, Zhang Weizhong, Zhu Guizhi, et al. Rethinking cancer nanotheranostics [J]. Nature Reviews Materials, 2017, 2: 17024.
[38] Albanese A, Lam AK, Sykes EA, et al. Tumour-on-a-chip provides an optical window into nanoparticle tissue transport [J]. Nat Commun, 2013, 4: 2718.
[39] Grainger SJ, Serna JV, Sunny S, et al. Pulsed ultrasound enhances nanoparticle penetration into breast cancer spheroids [J]. Mol. Pharmaceutics 2010, 7(6): 2006-2019.
[40] Huo Shuaidong, Ma Huili, Huang Keyang, et al. Superior penetration and retention behavior of 50 nm gold nanoparticles in tumors [J]. Cancer Res, 2013, 73(1): 319-330.
[41] Garcia I, Henriksen-Lacey M, Calvo J, et al. Size-dependent transport and cytotoxicity of mitomycin-gold nanoparticle conjugates in 2D and 3D mammalian cell models [J]. Bioconjug Chem, 2019, 30(1): 242-252.
[42] Bugno J, Hsu HJ, Pearson RM, et al. Size and surface charge of engineered poly(amidoamine) dendrimers modulate tumor accumulation and penetration: a model study using multicellular tumor spheroids [J]. Mol Pharm, 2016, 13(7): 2155-2163.
[43] Pilz M, Kwapiszewska K, Kalwarczyk T, et al. Transport of nanoprobes in multicellular spheroids [J]. Nanoscale, 2020, 12(38): 19880-19887.
[44] Agarwal R, Jurney P, Raythatha M, et al. Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models [J]. Adv Healthc Mater, 2015, 4(15): 2269-2280.
[45] Zhang Long, Wang Yong, Yang Dejun, et al. Shape effect of nanoparticles on tumor penetration in monolayers versus spheroids [J]. Mol Pharm, 2019, 16(7): 2902-2911.
[46] Kim B, Han G, Toley BJ, et al. Tuning payload delivery in tumour cylindroids using gold nanoparticles [J]. Nat Nanotechnol, 2010, 5(6): 465-472.
[47] Jin Shubin, Ma Xiaowei, Ma Huili, et al. Surface chemistry-mediated penetration and gold nanorod thermotherapy in multicellular tumor spheroids [J]. Nanoscale, 2013, 5(1): 143-146.
[48] Gaspar VM, Costa EC, Queiroz JA, et al. Folate-targeted multifunctional amino acid-chitosan nanoparticles for improved cancer therapy [J]. Pharm Res, 2015, 32(2): 562-577.
[49] Wang Yazhe, Xie Ying, Li Jing, et al. Tumor-penetrating nanoparticles for enhanced anticancer activity of combined photodynamic and hypoxia-activated therapy [J]. ACS Nano, 2017, 11(2): 2227-2238.
[50] Wang Tingting, Wang Dangge, Liu Jianping, et al. Acidity-triggered ligand-presenting nanoparticles to overcome sequential drug delivery barriers to tumors [J]. Nano Lett, 2017, 17(9): 5429-5436.
[51] Kolhar P, Anselmo AC, Gupta V, et al. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium [J]. Proc Natl Acad Sci USA, 2013, 110(26): 10753-10758.
[52] Shah S, Liu Y, Hu W, et al. Modeling particle shape-dependent dynamics in nanomedicine [J]. J Nanosci Nanotechnol, 2011, 11(2): 919-928.
[53] Suzuki S, Itakura S, Matsui R, et al. Tumor microenvironment-sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells and accompanying actin depolymerization [J]. Biomacromolecules, 2017, 18(2): 535-543.
[54] Mikhail AS, Allen C, Block copolymer micelles for delivery of cancer therapy: transport at the whole body, tissue and cellular levels [J]. J Control Release, 2009, 138(3): 214-223.
[55] Zhou Fangyuan, Feng Bing, Yu Haijun, et al. Cisplatin prodrug-conjugated gold nanocluster for fluorescence imaging and targeted therapy of the breast cancer [J]. Theranostics, 2016, 6(5): 679-687.
[56] Yokoi K, Kojic M, Milosevic M, et al. Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability into the tumor microenvironment [J]. Cancer Res, 2014, 74(16): 4239-4246.
[57] Ramanujan S, Pluen A, McKee TD, et al. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium [J]. Biophys J, 2002, 83(3): 1650-1660.
[58] Jain RK, Stylianopoulos T Delivering nanomedicine to solid tumors [J]. Nat Rev Clin Oncol, 2010, 7(11): 653-664.
[59] Dowd CJ, Cooney CL, Nugent MA Heparan sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding [J]. J Biol Chem, 1999, 274(8): 5236-5244.
[60] Priwitaningrum DL, Blonde JG, Sridhar A, et al. Tumor stroma-containing 3D spheroid arrays: a tool to study nanoparticle penetration [J]. J Control Release, 2016, 244(Pt B): 257-268.
[61] Wang Xin, Tang Huang, Wang Chongzhi, et al. Phenylboronic acid-mediated tumor targeting of chitosan nanoparticles [J]. Theranostics, 2016, 6(9): 1378-1392.
[62] Abdolahinia ED, Nadri S, Rahbarghazi R, et al. Enhanced penetration and cytotoxicity of metformin and collagenase conjugated gold nanoparticles in breast cancer spheroids [J]. Life Sci, 2019, 231: 116545.
[63] Du Yangyang, Han Mingda, Cao Kunxia, et al. Gold nanorods exhibit intrinsic therapeutic activity via controlling N6-methyladenosine-based epitranscriptomics in acute myeloid leukemia [J]. ACS Nano, 2021, 15(11): 17689-17704.
[64] Senyavina NV, Gerasimenko TN, Pulkova NV, et al. Transport and toxicity of silver nanoparticles in HepaRG cell spheroids [J]. Bull Exp Biol Med, 2016, 160(6): 831-834.
[65] Elje E, Mariussen E, Moriones OH, et al. Hepato(Geno)toxicity assessment of nanoparticles in a HepG2 liver spheroid model [J]. Nanomaterials (Basel), 2020, 10(3): 545.
[66] Dang Zechun, Sun Jizheng, Fan Jiaqi, et al. Zinc oxide spiky nanoparticles: a promising nanomaterial for killing tumor cells [J]. Mater Sci Eng C Mater Biol Appl, 2021, 124: 112071.
[67] Rozhina E, Danilushkina A, Akhatova F, et al. Biocompatibility of magnetic nanoparticles coating with polycations using A549 cells [J]. J Biotechnol, 2021, 325: 25-34.