Microfluidics for Cancer Nanomedicine: From Fabrication to Evaluation

Self-assembled drug delivery systems (sDDSs), made from nanocarriers and drugs, are one of the major types of nanomedicines, many of which are in clinical use, under preclinical investigation, or in clinical trials. One of the hurdles of this type of nanomedicine in real applications is the inherent complexity of their fabrication processes, which generally lack precise control over the sDDS structures and the batch-to-batch reproducibility. Furthermore, the classic 2D in vitro cell model, monolayer cell culture, has been used to evaluate sDDSs. However, 2D cell culture cannot adequately replicate in vivo tissue-level structures and their highly complex dynamic 3D environments, nor can it simulate their functions. Thus, evaluations using 2D cell culture often cannot correctly correlate with sDDS behaviors and effects in humans. Microfluidic technology offers novel solutions to overcome these problems and facilitates studying the structure-performance relationships for sDDS developments. In this Review, recent advances in microfluidics for 1) fabrication of sDDSs with well-defined physicochemical properties, such as size, shape, rigidity, and drug-loading efficiency, and 2) fabrication of 3D-cell cultures as tissue/organ-on-a-chip platforms for evaluations of sDDS biological performance are in focus.