Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells

Abstract

(1 of 17)www.global-challenges.com robotics, have promoted the use of in vitro tumor models in high-throughput drug screenings. [2,3] High-throughput screens for anticancer drugs have been, for a long time, limited to 2D culture of tumor cells, grown as a monolayer on the bottom of a well of a microtiter plate. Compared to 2D cell cultures, 3D culture systems can more faithfully model cell-cell interactions, matrix deposition and tumor microenvironments, including more physiological flow conditions, oxygen and nutrient gradients. [4] Therefore, 3D cultures have recently begun to be incorporated into high-throughput drug screenings, with the aim of better predicting drug efficacy and improving the prioritization of candidate drugs for further in vivo testing in animals.Because of the relatively simple, reproducible, amenable to automation and scalable culture methods, single-cell type and mixed-cell tumor spheroids, known as multicellular tumor spheroids (MCTSs), are used as 3D models. [5] There exists a broad range of natural hydrogels that are compatible with microfluidics, and which provide cancer cells with mechanical cues and adhesion sites to proliferate and grow into MCTSs. [6] With the aid of microfluidics and development of more complex 3D tumor models, [7,8] and the large-scale production of tumor spheroids in hydrogels, the number of compounds that could progress to in vivo testing could be restricted, thus reducing the number of animals needed for preclinical studies.Tumor-targeted drug delivery using microparticles and liposomes is beneficial compared to conventional drug administration. This is because encapsulated drug dosages can be controlled, healthy tissues can remain unharmed during treatment and drug resistance of cancer cells may be reduced/ prevented. [9,10] Microparticles and liposomes can be tailored to specifically target tumor sites using molecular conjugates, while avoiding toxic effects. [9] This review discusses the application of droplet-based microfluidic technologies for the development of accurate in vitro tumor models and improved cancer treatment strategies. The first part of the review centers around the generation of MCTSs in natural hydrogels for a better recapitulation of the in vivo tumor microenvironment. The second section is focused on microparticle and liposomal production for tumor-targeted drug delivery. Emphases is given to microfluidic methodologies for the production of these systems, and the potential of compartmentalized artificial cells as anticancer drug screening platforms.

Application of Artificial Intelligence to In Vitro Tumor Modeling and Characterization of the Tumor Microenvironment

“…[42] Highthroughput devices were thus devised based on this concept for biomedical applications such as tissue engineering, drug delivery systems, and high throughput analysis. [41][42][43][44][45][46] For instance, Lee et al devised a device for automated, large-scale generation of homogenous cell spheroids to successfully generate uniformly sized neural stem cell-derived neurospheres, [45] and Wang et al developed a highly efficient platform combined with lentivirus transduction system to functionally screen millions of antibodies to identify potential hits with desired functionalities for nextgeneration immunotherapy. [46] However, large dataset requires a large data-processing capacity.…”

Applications of Microfluidics and Organ-on-a-Chip in Cancer Research

“…These droplets can be utilized to encapsulate anti-cancer drugs as well as other molecules such as antibodies, proteins, growth factors, indicators, and macrophages for a variety of bio-applications, and they can be released by active or passive processes. These droplets can be created using microfluidic techniques, allowing for programmable drug absorption, confinement, and controlled release [ 100 ].…”

Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering

“…In this review, we focus on the most recent developments in microfluidics-assisted formulation of biomaterials, in particular on those with nontrivial internal architecture, typically consisting of multiple distinct compartments. ,− ,, We use the term “microfluidics” to describe a set of techniques aimed at developing of high-level of control over tiny liquid volumes, typically nano- or even picoliter volumes, at submillimeter length scale. In particular, microfluidics can be used to disperse hydrogel precursor solutions into monodisperse droplets or extrude them into stable jets, which subsequently solidify, either spontaneously or via externally triggered cross-linking reaction, into hydrogel microparticles, ,,,,,− microfibers, − or more general “microgels”.…”