Tumor-Microenvironment-on-a-Chip for Evaluating Nanoparticle-Loaded Macrophages for Drug Delivery

Abstract

Targeted drug delivery remains attractive but challenging for cancer therapy. Cell-mediated drug delivery has emerged as a promising strategy to improve targeted drug delivery to tumors due to the intrinsic ability of certain types of cells (e.g., macrophage) to pass through physiological barriers and specifically home to tumors. To fundamentally understand how macrophage-based drug carriers transport and interact with the tumor microenvironment, we developed a tumor-microenvironment-on-a-chip (TMOC) model that enables the coculture of tumor spheroids and macrophages in a three-dimensional (3D) gel matrix. By introducing drug-loaded macrophages, the TMOC model allows real-time observation of macrophage migration toward the tumor, infiltration into tumor spheroids, and subsequent response of tumor to drugs. Our results demonstrated the superior capability of macrophages migrating toward the tumor and infiltrate tumor spheroids. Drug loading in macrophages had minimum effect on their cell viability, and drug-carrying macrophages exhibited greater tumor cell cytotoxicity compared to their nanoparticle counterparts. Our work highlighted the great potential of macrophages as novel drug carriers for targeted drug delivery, and the TMOC model serves as a versatile platform to enable quick evaluation of such cell-mediated drug delivery systems.

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

“…Wang et al [ 60 ] developed a tumor-microenvironment-on-a-chip device for the co-culture of macrophages and ovarian adenocarcinoma spheroids in a 3D gel matrix. The macrophages served as carriers of PTX-loaded polymer nanoparticles.…”

“…Adapted with permission from [ 59 ]. ( c ) Tumor-microenvironment-on-a-chip developed by Wang et al [ 60 ] for drug-carrying macrophages and their delivery to tumors in vivo and in vitro: (VI) Schematic illustration, and (VII) Confocal images showing migration of RAW 264.7 cells (red) toward SKOV3 spheroids (green) in microfluidic channels on days 1, 3, and 5. Scale bars represent 200 μm.…”

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model

“…In order to achieve this, the traditional ''sandwich'' microfluidic design was chosen. 29 The selected microfluidic has a central chamber and two perfusable lateral channels. THP-1 cells encapsulated in Matrigel s were seeded in the left channel, hCH were seeded in the right channel, and NPs-Hydrogel was added in the central channel (Fig.…”

Controlled Surface Adhesion of Macrophages via Patterned Antifouling Polymer Brushes

“…[ 11,12 ] Thus, the development of platforms for selective capture that enable studying the behavior of specific subpopulations of macrophages are of high interest for diagnostics, treatment, and follow‐up of therapies. [ 13 ]…”

“…macrophages are of high interest for diagnostics, treatment, and follow-up of therapies. [13] One way to accomplish this task is to introduce surfaces that can selectively capture the targeted cells at precise locations while preventing nonspecific binding of other cells or other subpopulations. The specific capture is usually achieved by introducing receptors or ligands that are complementary to those expressed in the desired cells but orthogonal to others, while the prevention of unspecific adhesion demands to generate physical barriers that repel cells.…”