Recapitulation of complex transport and action of drugs at the tumor microenvironment using tumor-microenvironment-on-chip

Cancer Lett. 2016 Sep 28;380(1):319-29. doi: 10.1016/j.canlet.2015.12.003. Epub 2015 Dec 10.

Abstract

Targeted delivery aims to selectively distribute drugs to targeted tumor tissues but not to healthy tissues. This can address many clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, a complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicine. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery were discussed, and the current status and challenges for developing in vitro transport model systems were reviewed.

Keywords: Drug transport; Microfluidics; Nanoparticles; Stromal tissue; Targeted delivery.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biological Transport
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Proliferation / drug effects
  • Drug Carriers
  • Drug Delivery Systems / methods*
  • Drug Discovery / instrumentation
  • Drug Discovery / methods
  • Drug Resistance, Neoplasm
  • Humans
  • Lab-On-A-Chip Devices*
  • Microchip Analytical Procedures*
  • Microfluidic Analytical Techniques / instrumentation
  • Micromanipulation / instrumentation
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents
  • Drug Carriers