This Title All WIREs
How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high‐throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer‐related cell–cell and cell–matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug‐screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient‐specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Physiological barriers of tumor microenvironment affect delivery of NPs. Tumor tissue features an immature and leaky vasculature, compressed lymphatics, a dense ECM, and high interstitial fluid pressure (IFP) that act against the delivery and retention of NPs.
[ Normal View | Magnified View ]
Microfluidic technologies to evaluate transport of nanoparticles (NPs) during various steps of delivery to tumor. Blood‐borne transport: (A) endothelial cell monolayers cultured within microfluidic channels allow characterization of adhesion dynamics of nanoparticles to endothelium under systematic variation of flow conditions and associated shear stress. (Reprinted with permission from Ref . Copyright 2013 National Academy of Sciences) Transvascular transport: (B) in vitro vessel networks can be formed within hydrogels by vasculogenesis and/or angiogenesis within microfluidic devices and fulfill barrier function against extravasation of macromolecules. (Adapted from Ref with permission of The Royal Society of Chemistry. Copyright 2013) (C) The architecture of lumen structures can be precisely defined by casting hydrogels against microstructured molds. (Reprinted with permission from Ref . Copyright 2012 National Academy of Sciences) Interstitial transport: (D) Cancer cells cultured in microfluidic channels adjacent to flow simulate penetration of macromolecular drugs and NPs within dense tumor interstitium and enable comparison of drug accumulation under dynamic perfusion with plasma clearance. (Adapted from Ref with permission of The Royal Society of Chemistry. Copyright 2013)
[ Normal View | Magnified View ]
Scientific publication trends for contemporary in vitro tumor models. Records of original research publications matching ‘tumor spheroid model’ and ‘microfluidic tumor model’ keywords in their topics were retrieved from Web of Science citation index and plotted according to publication year. The cumulative number of records is indicated by gray‐scale symbols, whereas percentage of number of publications is indicated by colored symbols. The graph shows the years between 2000 and 2015.
[ Normal View | Magnified View ]
Modeling of multiscale biophysical phenomena for mechanistic understanding of nanoparticle (NP) transport. Pore‐level interactions of NPs with their surroundings determine the transport properties that are used as inputs of microvasculature‐ and tissue‐level continuum models for predictive simulation of NP transport. Parameters arising from tumor microenvironmental conditions and NP pharmacokinetics are also inputs to the continuum models.
[ Normal View | Magnified View ]

Browse by Topic

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts