Targeted Cancer Therapy-on-A-Chip

Abstract

Targeted cancer therapy (TCT) is gaining increased interest because it reduces the risks of adverse side effects by specifically treating tumor cells. TCT testing has traditionally been performed using two-dimensional (2D) cell culture and animal studies. Organ-on-a-chip (OoC) platforms have been developed to recapitulate cancer in vitro, as cancer-on-a-chip (CoC), and used for chemotherapeutics development and testing. This review explores the use of CoCs to both develop and test TCTs, with a focus on three main aspects, the use of CoCs to identify target biomarkers for TCT development, the use of CoCs to test free, un-encapsulated TCTs, and the use of CoCs to test encapsulated TCTs. Despite current challenges such as system scaling, and testing externally triggered TCTs, TCToC shows a promising future to serve as a supportive, pre-clinical platform to expedite TCT development and bench-to-bedside translation.

Keywords: 3D culture; chemotherapy; drug delivery; microfluidic; organ‐on‐a‐chip; targeting.

Figure 1

Exploring targeted cancer therapy‐on‐a‐chip (Created using BioRender.com).

Figure 2

Summary of Tumor Targeting Methods. GSH: glutathione, ROS: reactive oxygen species.

Figure 3

Summary of current methods for testing targeting. 2D: two‐dimensional, 3D: three‐dimensional.

Figure 4

Single‐ and multi‐organ metastasis‐on‐a‐chip platforms i) Schematic diagram of 3D‐CMOM system with description of the function of each area on the chip. Reproduced with permission.^{[ 90 ]} Copyright 2021, ACS Publications. ii) Design of a multi‐organs‐on‐a‐chip to mimic lung cancer metastasis and in vivo validation of system performance. Reproduced with permission.^{[ 247 ]} Copyright 2016, ACS Publications.

Figure 5

Evaluating targeted chemotherapeutics in CoC models (Created using BioRender.com). HER2: Human epidermal growth factor receptor 2, VEGF: Vascular endothelial growth factor, EGFR: Epidermal growth factor receptor.

Figure 6

The use of OoCs and MoCs in the investigation and evaluation of targeted drug delivery systems through passive, active, and triggered targeting strategies. i) In vitro regulation of cancer angiogenesis using a 3D microfluidic platform using MSNs loaded with or without siVEGF or siVEGFR. Adapted from^{[ 80 ]} with permission from ACS Publications. ii) A microfluidic device for encapsulating cancer cells in core–shell microcapsules, which form microtumors after incubation for 10 days, and testing NIR activated NPs. Staining for ACTIN filament, CD31, and cell nuclei showed extensive vascularization of the 3D tumors. Reproduced with permission.^{[ 101 ]} Copyright 2017, ACS Publications.