Microfluidic-Based Platform for the Evaluation of Nanomaterial-Mediated Drug Delivery: From High-Throughput Screening to Dynamic Monitoring

Author(s): Yamin Yang*, Sijia Liu, Jinfa Geng

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 27 , 2019

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Nanomaterial-based drug delivery holds tremendous promise for improving targeting capacity, biodistribution, and performance of therapeutic/diagnostic agents. Accelerating the clinical translation of current nanomedicine requires an in-depth understanding of the mechanism underlying the dynamic interaction between nanomaterials and cells in a physiological/pathophysiological-relevant condition. The introduction of the advanced microfluidic platform with miniaturized, well-controlled, and high-throughput features opens new investigation and application opportunities for nanomedicine evaluation. This review highlights the current state-of-theart in the field of 1) microfluidic-assisted in vitro assays that are capable of providing physiological-relevant flow conditions and performing high-throughput drug screening, 2) advanced organ-on-a-chip technology with the combination of microfabrication and tissue engineering techniques for mimicking microenvironment and better predicting in vivo response of nanomedicine, and 3) the integration of microdevice with various detection techniques that can monitor cell-nanoparticle interaction with high spatiotemporal resolution. Future perspectives regarding optimized on-chip disease modeling and personalized nanomedicine screening are discussed towards further expanding the utilization of the microfluidic-based platform in assessing the biological behavior of nanomaterials.

Keywords: Nanomedicine, microfluidic, drug evaluation, organ-on-chip, nanoparticle, drug delivery.

Youn YS, Bae YH. Perspectives on the past, present, and future of cancer nanomedicine. Adv Drug Deliv Rev 2018; 130: 3-11.
[http://dx.doi.org/10.1016/j.addr.2018.05.008] [PMID: 29778902]
Rizzo LY, Theek B, Storm G, Kiessling F, Lammers T. Recent progress in nanomedicine: Therapeutic, diagnostic and theranostic applications. Curr Opin Biotechnol 2013; 24(6): 1159-66.
[http://dx.doi.org/10.1016/j.copbio.2013.02.020] [PMID: 23578464]
Venugopal J, Prabhakaran MP, Low S, et al. Nanotechnology for nanomedicine and delivery of drugs. Curr Pharm Des 2008; 14(22): 2184-200.
[http://dx.doi.org/10.2174/138161208785740180] [PMID: 18781971]
Teli MK, Mutalik S, Rajanikant GK. Nanotechnology and nanomedicine: Going small means aiming big. Curr Pharm Des 2010; 16(16): 1882-92.
[http://dx.doi.org/10.2174/138161210791208992] [PMID: 20222866]
Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: Progress, challenges and opportunities. Nat Rev Cancer 2017; 17(1): 20-37.
[http://dx.doi.org/10.1038/nrc.2016.108] [PMID: 27834398]
Tran S, DeGiovanni P-J, Piel B, Rai P. Cancer nanomedicine: A review of recent success in drug delivery. Clin Transl Med 2017; 6(1): 44.
[http://dx.doi.org/10.1186/s40169-017-0175-0] [PMID: 29230567]
Min Y, Caster JM, Eblan MJ, Wang AZ. Clinical translation of nanomedicine. Chem Rev 2015; 115(19): 11147-90.
[http://dx.doi.org/10.1021/acs.chemrev.5b00116] [PMID: 26088284]
Paradise J. Regulating nanomedicine at the food and drug administration. AMA J Ethics 2019; 21(4): E347-55.
[http://dx.doi.org/10.1001/amajethics.2019.347] [PMID: 31012422]
Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR. Nanoparticle-based medicines: A review of FDA-approved materials and clinical trials to date. Pharm Res 2016; 33(10): 2373-87.
[http://dx.doi.org/10.1007/s11095-016-1958-5] [PMID: 27299311]
Zhang X-Q, Xu X, Bertrand N, Pridgen E, Swami A, Farokhzad OC. Interactions of nanomaterials and biological systems: Implications to personalized nanomedicine. Adv Drug Deliv Rev 2012; 64(13): 1363-84.
[http://dx.doi.org/10.1016/j.addr.2012.08.005] [PMID: 22917779]
Lombardo D, Kiselev MA, Caccamo MT. Smart nanoparticles for drug delivery application: Development of versatile nanocarrier platforms in biotechnology and nanomedicine. J Nanomater 2019; 2019: 1-26.
Sheth P, Sandhu H, Singhal D, Malick W, Shah N, Kislalioglu MS. Nanoparticles in the pharmaceutical industry and the use of supercritical fluid technologies for nanoparticle production. Curr Drug Deliv 2012; 9(3): 269-84.
[http://dx.doi.org/10.2174/156720112800389052] [PMID: 22283656]
Leuenberger H. New trends in the production of pharmaceutical granules: The classical batch concept and the problem of scale-up. Eur J Pharm Biopharm 2001; 52(3): 279-88.
[http://dx.doi.org/10.1016/S0939-6411(01)00200-4] [PMID: 11677070]
Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: The past and the future. Adv Drug Deliv Rev 2013; 65(1): 104-20.
[http://dx.doi.org/10.1016/j.addr.2012.10.003] [PMID: 23088863]
Anchordoquy TJ, Barenholz Y, Boraschi D, et al. Mechanisms and barriers in cancer nanomedicine: Addressing challenges, looking for solutions. ACS Nano 2017; 11(1): 12-8.
[http://dx.doi.org/10.1021/acsnano.6b08244] [PMID: 28068099]
Dai Q, Wilhelm S, Ding D, et al. Quantifying the ligand-coated nanoparticle delivery to cancer cells in solid tumors. ACS Nano 2018; 12(8): 8423-35.
[http://dx.doi.org/10.1021/acsnano.8b03900] [PMID: 30016073]
Wilhelm S, Tavares AJ, Dai Q, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater 2016; 1: 16014.
Almeida JPM, Chen AL, Foster A, Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine (Lond) 2011; 6(5): 815-35.
[http://dx.doi.org/10.2217/nnm.11.79] [PMID: 21793674]
Yildirimer L, Thanh NTK, Loizidou M, Seifalian AM. Toxicological considerations of clinically applicable nanoparticles. Nano Today 2011; 6: 585-607.
[http://dx.doi.org/10.1016/j.nantod.2011.10.001] [PMID: 23293661]
Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 2009; 61(6): 428-37.
[http://dx.doi.org/10.1016/j.addr.2009.03.009] [PMID: 19376175]
Teeguarden JG, Hinderliter PM, Orr G, Thrall BD, Pounds JG. Particokinetics in vitro: dosimetry considerations for in vitro nanoparticle toxicity assessments. Toxicol Sci 2007; 95(2): 300-12.
[http://dx.doi.org/10.1093/toxsci/kfl165] [PMID: 17098817]
Chou LYT, Ming K, Chan WCW. Strategies for the intracellular delivery of nanoparticles. Chem Soc Rev 2011; 40(1): 233-45.
[http://dx.doi.org/10.1039/C0CS00003E] [PMID: 20886124]
Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 2012; 41(7): 2545-61.
[http://dx.doi.org/10.1039/c2cs15327k] [PMID: 22334259]
Lazzari G, Couvreur P, Mura S. Multicellular tumor spheroids: a relevant 3D model for the in vitro preclinical investigation of polymer nanomedicines. Polym Chem 2017; 8: 4947-69.
Huang B-W, Gao J-Q. Application of 3D cultured multicellular spheroid tumor models in tumor-targeted drug delivery system research. J Control Release 2018; 270: 246-59.
[http://dx.doi.org/10.1016/j.jconrel.2017.12.005] [PMID: 29233763]
Le V-M, Lang M-D, Shi W-B, Liu J-W. A collagen-based multicellular tumor spheroid model for evaluation of the efficiency of nanoparticle drug delivery. Artif Cells Nanomed Biotechnol 2016; 44(2): 540-4.
[http://dx.doi.org/10.3109/21691401.2014.968820] [PMID: 25315504]
Fontana F, Martins JP, Torrieri G, Santos HA. Nuts and bolts: microfluidics for the production of biomaterials. Adv Mater Technol 800611
Karnik R, Gu F, Basto P, et al. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett 2008; 8(9): 2906-12.
[http://dx.doi.org/10.1021/nl801736q] [PMID: 18656990]
Liu D, Cito S, Zhang Y, Wang CF, Sikanen TM, Santos HA. A versatile and robust microfluidic platform toward high throughput synthesis of homogeneous nanoparticles with tunable properties. Adv Mater 2015; 27(14): 2298-304.
[http://dx.doi.org/10.1002/adma.201405408] [PMID: 25684077]
Ma J, Lee SMY, Yi C, Li CW. Controllable synthesis of functional nanoparticles by microfluidic platforms for biomedical applications -a review. Lab Chip 2017; 17(2): 209-26.
[http://dx.doi.org/10.1039/C6LC01049K] [PMID: 27991629]
Valencia PM, Farokhzad OC, Karnik R, Langer R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol 2012; 7(10): 623-9.
[http://dx.doi.org/10.1038/nnano.2012.168] [PMID: 23042546]
Giridharan V, Yun Y, Hajdu P, et al. Microfluidic platforms for evaluation of nanobiomaterials: A review. J Nanomater 2012; 2012789841
Mccormick SC, Kriel FH, Ivask A, et al. The use of microfluidics in cytotoxicity and nanotoxicity experiments. Micromachines (Basel) 2017; 8: 124.
He Z, Ranganathan N, Li P. Evaluating nanomedicine with microfluidics. Nanotechnology 2018; 29(49)492001
[http://dx.doi.org/10.1088/1361-6528/aae18a] [PMID: 30215611]
Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol 2014; 32(8): 760-72.
[http://dx.doi.org/10.1038/nbt.2989] [PMID: 25093883]
Zhang B, Korolj A, Fook B, et al. Advances in organ-on-a-chip engineering. Nat Rev Mater 2018; 3: 257-78.
Bhise NS, Ribas J, Manoharan V, et al. Organ-on-a-chip platforms for studying drug delivery systems. J Control Release 2014; 190: 82-93.
[http://dx.doi.org/10.1016/j.jconrel.2014.05.004] [PMID: 24818770]
Yager P, Edwards T, Fu E, et al. Microfluidic diagnostic technologies for global public health. Nature 2006; 442(7101): 412-8.
[http://dx.doi.org/10.1038/nature05064] [PMID: 16871209]
Mahto SK, Charwat V, Ertl P, Rothen-Rutishauser B, Rhee SW, Sznitman J. Microfluidic platforms for advanced risk assessments of nanomaterials. Nanotoxicology 2015; 9(3): 381-95.
[http://dx.doi.org/10.3109/17435390.2014.940402] [PMID: 25051329]
Sung JH, Kam C, Shuler ML. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 2010; 10(4): 446-55.
[http://dx.doi.org/10.1039/b917763a] [PMID: 20126684]
Nge PN, Rogers CI, Woolley AT. Advances in microfluidic materials, functions, integration, and applications. Chem Rev 2013; 113(4): 2550-83.
[http://dx.doi.org/10.1021/cr300337x] [PMID: 23410114]
McDonald JC, Duffy DC, Anderson JR, et al. Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis 2000; 21(1): 27-40.
[http://dx.doi.org/10.1002/(SICI)1522-2683(20000101)21:1<27:AID-ELPS27>3.0.CO;2-C] [PMID: 10634468]
Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 2000; 288(5463): 113-6.
[http://dx.doi.org/10.1126/science.288.5463.113] [PMID: 10753110]
Zhang S, Gao H, Bao G. Physical principles of nanoparticle cellular endocytosis. ACS Nano 2015; 9(9): 8655-71.
[http://dx.doi.org/10.1021/acsnano.5b03184] [PMID: 26256227]
Freese C, Schreiner D, Anspach L, et al. In vitro investigation of silica nanoparticle uptake into human endothelial cells under physiological cyclic stretch. Part Fibre Toxicol 2014; 11: 68.
[http://dx.doi.org/10.1186/s12989-014-0068-y] [PMID: 25539809]
Wittmaack K. Excessive delivery of nanostructured matter to submersed cells caused by rapid gravitational settling. ACS Nano 2011; 5(5): 3766-78.
[http://dx.doi.org/10.1021/nn200112u] [PMID: 21446668]
Wills JW, Summers HD, Hondow N, et al. Characterizing nanoparticles in biological matrices: Tipping points in agglomeration state and cellular delivery in vitro. ACS Nano 2017; 11(12): 11986-2000.
[http://dx.doi.org/10.1021/acsnano.7b03708] [PMID: 29072897]
Grabinski C, Sharma M, Maurer E, Sulentic C, Mohan Sankaran R, Hussain S. The effect of shear flow on nanoparticle agglomeration and deposition in in vitro dynamic flow models. Nanotoxicology 2016; 10(1): 74-83.
[PMID: 25961858]
Chiu DT, DeMello AJ, Di Carlo D, et al. Small butperfectly formed? successes, challenges, and opportunities for microfluidics in the chemical and biological sciences. Chem 2017; 2: 201-23.
Wong KHK, Chan JM, Kamm RD, Tien J. Microfluidic models of vascular functions. Annu Rev Biomed Eng 2012; 14: 205-30.
[http://dx.doi.org/10.1146/annurev-bioeng-071811-150052] [PMID: 22540941]
Smith Q, Gerecht S. Going with the flow: microfluidic platforms in vascular tissue engineering. Curr Opin Chem Eng 2014; 3: 42-50.
[http://dx.doi.org/10.1016/j.coche.2013.11.001] [PMID: 24644533]
Chen H, Yu Z, Bai S, et al. Microfluidic models of physiological or pathological flow shear stress for cell biology, disease modeling and drug development. TrAC Trends Anal Chem In press
Kim S, Chung M, Ahn J, Lee S, Jeon NL. Interstitial flow regulates the angiogenic response and phenotype of endothelial cells in a 3D culture model. Lab Chip 2016; 16(21): 4189-99.
[http://dx.doi.org/10.1039/C6LC00910G] [PMID: 27722679]
Riaz N, Wolden SL, Gelblum DY, Eric J. Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication. Lab Chip 2016; 118: 6072-8.
Farokhzad OC, Khademhosseini A, Jon S, et al. Microfluidic system for studying the interaction of nanoparticles and microparticles with cells. Anal Chem 2005; 77(17): 5453-9.
[http://dx.doi.org/10.1021/ac050312q] [PMID: 16131052]
Klingberg H, Loft S, Oddershede LB, Møller P. The influence of flow, shear stress and adhesion molecule targeting on gold nanoparticle uptake in human endothelial cells. Nanoscale 2015; 7(26): 11409-19.
[http://dx.doi.org/10.1039/C5NR01467K] [PMID: 26077188]
Fede C, Albertin G, Petrelli L, et al. Influence of shear stress and size on viability of endothelial cells exposed to gold nanoparticles. J Nanopart Res 2017; 19(9): 316.
[http://dx.doi.org/10.1007/s11051-017-3993-5] [PMID: 28959137]
Mahto SK, Yoon TH, Rhee SW. A new perspective on in vitro assessment method for evaluating quantum dot toxicity by using microfluidics technology. Biomicrofluidics 2010; 4(3)034111
[http://dx.doi.org/10.1063/1.3486610] [PMID: 20957065]
Mahto SK, Yoon TH, Rhee SW. Cytotoxic effects of surface-modified quantum dots on neuron-like PC12 cells cultured inside microfluidic devices. Biochip J 2010; 4: 82-8.
Korin N, Kanapathipillai M, Matthews BD, et al. Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 2012; 337(6095): 738-42.
[http://dx.doi.org/10.1126/science.1217815] [PMID: 22767894]
Zheng W, Jiang B, Wang D, Zhang W, Wang Z, Jiang X. A microfluidic flow-stretch chip for investigating blood vessel biomechanics. Lab Chip 2012; 12(18): 3441-50.
[http://dx.doi.org/10.1039/c2lc40173h] [PMID: 22820518]
Freese C, Schreiner D, Anspach L, et al. In vitro investigation of silica nanoparticle uptake into human endothelial cells under physiological cyclic stretch. Part Fibre Toxicol 2014; 11: 68.
[http://dx.doi.org/10.1186/s12989-014-0068-y] [PMID: 25539809]
Moshksayan K, Kashaninejad N, Warkiani ME, et al. Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture. Sens Actuators B Chem 2018; 263: 151-76.
Narayanamurthy V, Nagarajan S, Firus Khan AY, et al. Microfluidic hydrodynamic trapping for single cell analysis: mechanisms, methods and applications. Anal Methods 2017; 9: 3751-72.
Zheng X, Tian J, Weng L, et al. Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip. Nanotechnology 2012; 23(5)055102
[http://dx.doi.org/10.1088/0957-4484/23/5/055102] [PMID: 22238256]
Wu J, Li H, Chen Q, et al. Statistical single-cell analysis of cell cycle- dependent quantum dot cytotoxicity and cellular uptake using a microfluidic system. RSC Advances 2014; 4: 24929-34.
Wu LY, Di Carlo D, Lee LP. Microfluidic self-assembly of tumor spheroids for anticancer drug discovery. Biomed Microdevices 2008; 10(2): 197-202.
[http://dx.doi.org/10.1007/s10544-007-9125-8] [PMID: 17965938]
Kim C, Bang JH, Kim YE, Lee SH, Kang JY. On-chip anticancer drug test of regular tumor spheroids formed in microwells by a distributive microchannel network. Lab Chip 2012; 12(20): 4135-42.
[http://dx.doi.org/10.1039/c2lc40570a] [PMID: 22864534]
Kwon S, Cho CH, Kwon Y, Lee ES, Park JK. A microfluidic immunostaining system enables quality assured and standardized immunohistochemical biomarker analysis. Sci Rep 2017; 7: 45968.
[http://dx.doi.org/10.1038/srep45968] [PMID: 28378835]
Jeong GS, Han S, Shin Y, et al. Sprouting angiogenesis under a chemical gradient regulated by interactions with an endothelial monolayer in a microfluidic platform. Anal Chem 2011; 83(22): 8454-9.
[http://dx.doi.org/10.1021/ac202170e] [PMID: 21985643]
Dertinger SKW, Chiu DT, Jeon NL, et al. Generation of gradients having complex shapes using microfluidic networks. Anal Chem 2001; 73: 1240-6.
Wang X, Liu Z, Pang Y. Concentration gradient generation methods based on microfluidic systems. RSC Advances 2017; 7: 29966-84.
Choe H, Nho HW, Park J, et al. Real-time monitoring of colloidal nanoparticles using light sheet dark-field microscopy combined with microfluidic concentration gradient generator(µFCGG-LSDFM). Bull Korean Chem Soc 2014; 35: 365-70.
Zhao L, Cheng P, Li J, et al. Analysis of nonadherent apoptotic cells by a quantum dots probe in a microfluidic device for drug screening. Anal Chem 2009; 81(16): 7075-80.
[http://dx.doi.org/10.1021/ac901121f] [PMID: 19634888]
Cunha-Matos CA, Millington OR, Wark AW, Zagnoni M. Real-time assessment of nanoparticle-mediated antigen delivery and cell response. Lab Chip 2016; 16(17): 3374-81.
[http://dx.doi.org/10.1039/C6LC00599C] [PMID: 27455884]
Markman JL, Rekechenetskiy A, Holler E, Ljubimova JY. Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv Drug Deliv Rev 2013; 65(13-14): 1866-79.
[http://dx.doi.org/10.1016/j.addr.2013.09.019] [PMID: 24120656]
Upreti M, Jyoti A, Sethi P. Tumor microenvironment and nanotherapeutics. Transl Cancer Res 2013; 2(4): 309-19.
[PMID: 24634853]
Gong X, Lin C, Cheng J, et al. Generation ofmulticellular tumor spheroids with microwell-based agarose scaffolds for drug testing. PLoS One 2015; 10(6)e0130348
[http://dx.doi.org/10.1371/journal.pone.0130348] [PMID: 26090664]
Lazzari G, Couvreur P, Mura S. Multicellular tumor spheroids: A relevant 3D model for the in vitro preclinical investigation of polymer nanomedicines. Polym Chem 2017; 8: 4947-69.
Lu H, Stenzel MH. Multicellular tumor spheroids (MCTS) as a 3D in vitro evaluation tool of nanoparticles. Small 2018; 14(13)e1702858
[http://dx.doi.org/10.1002/smll.201702858] [PMID: 29450963]
Le V-M, Lang M-D, Shi W-B, Liu J-W. A collagen-based multicellular tumor spheroid model for evaluation of the efficiency of nanoparticle drug delivery. Artif Cells Nanomed Biotechnol 2016; 44(2): 540-4.
[http://dx.doi.org/10.3109/21691401.2014.968820] [PMID: 25315504]
Yang Y, Yang X, Zou J, et al. Evaluation of photodynamic therapy efficiency using an in vitro three-dimensional microfluidic breast cancer tissue model. Lab Chip 2015; 15(3): 735-44.
[http://dx.doi.org/10.1039/C4LC01065E] [PMID: 25428803]
Tsai H-F, Trubelja A, Shen AQ, Bao G. Tumour-on-a-chip: Microfluidic models of tumour morphology, growth and microenvironment. J R Soc Interface 2017; 14(131)20170137
[http://dx.doi.org/10.1098/rsif.2017.0137] [PMID: 28637915]
Sontheimer-Phelps A, Hassell BA, Ingber DE. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer 2019; 19(2): 65-81.
[http://dx.doi.org/10.1038/s41568-018-0104-6] [PMID: 30647431]
Hachey SJ, Hughes CCW. Applications of tumor chip technology. Lab Chip 2018; 18(19): 2893-912.
[http://dx.doi.org/10.1039/C8LC00330K] [PMID: 30156248]
Portillo-Lara R, Annabi N. Microengineered cancer-on-a-chip platforms to study the metastatic microenvironment. Lab Chip 2016; 16(21): 4063-81.
[http://dx.doi.org/10.1039/C6LC00718J] [PMID: 27605305]
Albanese A, Lam AK, Sykes EA, Rocheleau JV, Chan WC. Tumour-on-a-chip provides an optical window into nanoparticle tissue transport. Nat Commun 2013; 4: 2718.
[http://dx.doi.org/10.1038/ncomms3718] [PMID: 24177351]
Kwak B, Ozcelikkale A, Shin CS, Park K, Han B. Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip. J Control Release 2014; 194: 157-67.
[http://dx.doi.org/10.1016/j.jconrel.2014.08.027] [PMID: 25194778]
Cicha I. Strategies to enhance nanoparticle-endothelial interactions under flow. J Cell Biotechnol 2016; 1: 191-208.
Huang RB, Mocherla S, Heslinga MJ, Charoenphol P, Eniola-Adefeso O. Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery. (review) Mol Membr Biol 2010; 27(4-6): 190-205.
[http://dx.doi.org/10.3109/09687688.2010.499548] [PMID: 20615080]
Golombek SK, May J-N, Theek B, et al. Tumor targeting via EPR: Strategies to enhance patient responses. Adv Drug Deliv Rev 2018; 130: 17-38.
[http://dx.doi.org/10.1016/j.addr.2018.07.007] [PMID: 30009886]
Kobayashi H, Watanabe R, Choyke PL. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics 2013; 4(1): 81-9.
[http://dx.doi.org/10.7150/thno.7193] [PMID: 24396516]
Bazak R, Houri M, Achy SE, Hussein W, Refaat T. Passive targeting of nanoparticles to cancer: A comprehensive review of the literature. Mol Clin Oncol 2014; 2(6): 904-8.
[http://dx.doi.org/10.3892/mco.2014.356] [PMID: 25279172]
Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 2016; 27(10): 2225-38.
[http://dx.doi.org/10.1021/acs.bioconjchem.6b00437] [PMID: 27547843]
Wang X, Sun Q, Pei J. Microfluidic-based 3D engineered microvascular networks and their applications in vascularized microtumor models. Micromachines (Basel) 2018; 9(10): 493.
[http://dx.doi.org/10.3390/mi9100493] [PMID: 30424426]
Lin DSY, Guo F, Zhang B. Modeling organ-specific vasculature with organ-on-a-chip devices. Nanotechnology 2019; 30(2)024002
[http://dx.doi.org/10.1088/1361-6528/aae7de] [PMID: 30395536]
Kim Y, Lobatto ME, Kawahara T, et al. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis. Proc Natl Acad Sci USA 2014; 111(3): 1078-83.
[http://dx.doi.org/10.1073/pnas.1322725111] [PMID: 24395808]
Vu MN, Rajasekhar P, Poole DP, et al. Rapid assessment of nanoparticle extravasation in a microfluidic tumor model. ACS Appl Nano Mater 2019; 2: 1844-56.
Zhang M, Xu C, Jiang L, Qin J. A 3D human lung-on-a-chip model for nanotoxicity testing. Toxicol Res (Camb) 2018; 7(6): 1048-60.
[http://dx.doi.org/10.1039/C8TX00156A] [PMID: 30510678]
Hassell BA, Goyal G, Lee E, et al. Human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro. Cell Rep 2017; 21(2): 508-16.
[http://dx.doi.org/10.1016/j.celrep.2017.09.043] [PMID: 29020635]
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010; 328(5986): 1662-8.
[http://dx.doi.org/10.1126/science.1188302] [PMID: 20576885]
Oddo A, Peng B, Tong Z, et al. Advances in microfluidic blood– brain barrier (BBB) models Trends Biotechnol 2019; S0167-7799: 30084-8.
Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng 2017; 114(1): 184-94.
[http://dx.doi.org/10.1002/bit.26045] [PMID: 27399645]
Yeon JH, Na D, Choi K, Ryu SW, Choi C, Park JK. Reliable permeability assay system in a microfluidic device mimicking cerebral vasculatures. Biomed Microdevices 2012; 14(6): 1141-8.
[http://dx.doi.org/10.1007/s10544-012-9680-5] [PMID: 22821236]
Bonakdar M, Graybill PM, Davalos RV. A microfluidic model of the blood-brain barrier to study permeabilization by pulsed electric fields. RSC Advances 2017; 7(68): 42811-8.
[http://dx.doi.org/10.1039/C7RA07603G] [PMID: 29308191]
Zhou Y, Peng Z, Seven ES, Leblanc RM. Crossing the blood-brain barrier with nanoparticles. J Control Release 2018; 270: 290-303.
[http://dx.doi.org/10.1016/j.jconrel.2017.12.015] [PMID: 29269142]
Papademetriou I, Vedula E, Charest J, Porter T. Effect of flow on targeting and penetration of angiopep-decorated nanoparticles in a microfluidic model blood-brain barrier. PLoS One 2018; 13(10)e0205158
[http://dx.doi.org/10.1371/journal.pone.0205158] [PMID: 30300391]
Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WCW. Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination. J Control Release 2016; 240: 332-48.
[http://dx.doi.org/10.1016/j.jconrel.2016.01.020] [PMID: 26774224]
Prot JM, Aninat C, Griscom L, et al. Improvement of HepG2/C3a cell functions in a microfluidic biochip. Biotechnol Bioeng 2011; 108(7): 1704-15.
[http://dx.doi.org/10.1002/bit.23104] [PMID: 21337338]
Prot JM, Briffaut AS, Letourneur F, et al. Integrated proteomic and transcriptomic investigation of the acetaminophen toxicity in liver microfluidic biochip. PLoS One 2011; 6(8)e21268
[http://dx.doi.org/10.1371/journal.pone.0021268] [PMID: 21857903]
Yu F, Deng R, Hao Tong W, et al. A perfusion incubator liver chip for 3D cell culture with application on chronic hepatotoxicity testing. Sci Rep 2017; 7(1): 14528.
[http://dx.doi.org/10.1038/s41598-017-13848-5] [PMID: 29109520]
Lee PJ, Hung PJ, Lee LP. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 2007; 97(5): 1340-6.
[http://dx.doi.org/10.1002/bit.21360] [PMID: 17286266]
Esch MB, Mahler GJ, Stokol T, Shuler ML. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 2014; 14(16): 3081-92.
[http://dx.doi.org/10.1039/C4LC00371C] [PMID: 24970651]
Du B, Yu M, Zheng J. Transport and interactions of nanoparticles in the kidneys. Nat Rev Mater 2018; 3: 358-74.
Jang KJ, Mehr AP, Hamilton GA, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol 2013; 5(9): 1119-29.
[http://dx.doi.org/10.1039/c3ib40049b] [PMID: 23644926]
Jang KJ, Suh KY. A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 2010; 10(1): 36-42.
[http://dx.doi.org/10.1039/B907515A] [PMID: 20024048]
Weber EJ, Chapron A, Chapron BD, et al. Development of a microphysiological model of human kidney proximal tubule function. Kidney Int 2016; 90(3): 627-37.
[http://dx.doi.org/10.1016/j.kint.2016.06.011] [PMID: 27521113]
Luongo K, Holton A, Kaushik A, et al. Microfluidic device for trapping and monitoring three dimensional multicell spheroids using electrical impedance spectroscopy. Biomicrofluidics 2013; 7(3): 34108.
[http://dx.doi.org/10.1063/1.4809590] [PMID: 24404028]
Hondroulis E, Liu C, Li CZ. Whole cell based electrical impedance sensing approach for a rapid nanotoxicity assay. Nanotechnology 2010; 21(31)315103
[http://dx.doi.org/10.1088/0957-4484/21/31/315103] [PMID: 20622302]
Richter L, Charwat V, Jungreuthmayer C, Bellutti F, Brueckl H, Ertl P. Monitoring cellular stress responses to nanoparticles using a lab-on-a-chip. Lab Chip 2011; 11(15): 2551-60.
[http://dx.doi.org/10.1039/c1lc20256a] [PMID: 21687846]
Rothbauer M, Praisler I, Docter D, Stauber RH, Ertl P. Microfluidic impedimetric cell regeneration assay to monitor the enhanced cytotoxic effect of nanomaterial perfusion. Biosensors (Basel) 2015; 5(4): 736-49.
[http://dx.doi.org/10.3390/bios5040736] [PMID: 26633532]
Syme CD, Sirimuthu NMS, Faley SL, Cooper JM. SERS mapping of nanoparticle labels in single cells using a microfluidic chip. Chem Commun (Camb) 2010; 46(42): 7921-3.
[http://dx.doi.org/10.1039/c0cc02209h] [PMID: 20859575]
Zhai Z, Zhang F, Chen X, et al. Uptake of silver nanoparticles by DHA-treated cancer cells examined by surface-enhanced Raman spectroscopy in a microfluidic chip. Lab Chip 2017; 17(7): 1306-13.
[http://dx.doi.org/10.1039/C7LC00053G] [PMID: 28247889]
Parthasarathy AB, Shin WG, Zhang XJ, Dunn AK. Laser speckle contrast imaging of flow in a microfluidic device. Proc SPIE - Int Soc Opt Eng. 2007; 644604
Wu Q, Ren W, Yu Z, Dong E, Zhang S, Xu RX. Microfabrication of polydimethylsiloxane phantoms to simulate tumor hypoxia and vascular anomaly. J Biomed Opt 2015; 20(12)121308
[http://dx.doi.org/10.1117/1.JBO.20.12.121308] [PMID: 26456687]
Yang Y, Lü A, Li W, Qian Z. Microfluidic-based laser speckle contrast imaging of erythrocyte flow and magnetic nanoparticle retention in blood. AIP Adv 2019.9015003

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Year: 2019
Page: [2953 - 2968]
Pages: 16
DOI: 10.2174/1381612825666190730100051
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