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

Abstract

Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, 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 medicines. 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 was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed.

3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype and serves as a critical design parameter for phenotypic models of EMT

“…The present work focused on 3D tumor-ECM model development, emphasizing the need for more accurate recapitulation of the PDAC desmoplastic ECM composition and microstructure, which is typically characterized by high levels of fibrillar type I collagen [ 53 ]. This fibrous, stiff ECM microenvironment is generally thought to compromise drug transport, decrease tumor chemosensitivity, and enhance EMT and tumor invasion [ 4 , 6 , 54 ]. However, our 3D tumor-ECM model revealed that PDAC phenotype and behavior vary significantly with initial tumor cell phenotype and depend largely on both the biochemical and biophysical properties of the surrounding stromal ECM.…”

In vitromicrofluidic models of tumor microenvironment to screen transport of drugs and nanoparticles

“…This underachievement is mainly attributed to current NP designs, which do not adequately address complex transport barriers around tumors. Delivery of NPs to tumor is a multistep process where each step involves interrelated multiple physiological barriers that hinder the transport and shows the potential to be the bottleneck for effective delivery of NP . Current delivery strategies of NPs involve tailoring of NP properties as well as modulation of the tumor microenvironment to alleviate the physiological barriers.…”

3D Immunocompetent Organ‐on‐a‐Chip Models

“…[ 128,129 ] In addition, the tumor stromal tissues represent the dynamic source of a variety of cytokines and growth factors that influence tumor progression and drug. [ 130 ] The interactions between the cancer cells and the stroma affect different aspects of tumor behaviors such as tumorigenesis, tumor invasion, metastasis, angiogenesis, and resistance to therapeutic agents. [ 127,129 ] Biomolecules produced by cancerous or stromal cells mediate the dynamics of solid tumors.…”