Advanced in vitro systems for efficacy and toxicity testing in nanomedicine

Abstract

The use of nanoparticles (NPs) in nanomedicine is becoming an established therapeutic strategy for transport and delivery of bioactive molecules across biological barriers to elicit a specific cytological response in a target cell population. The utility of NP-derivatised nanomedicines and their potential therapeutic benefits, together with their biosafety, are being explored in cell models that, in order to accurately predict clinical potential, must reflect the architecture and function of the tissues from which the cells originate. These cell-based models, and their application in preclinical nanomedicine, are the subject of this review. Models are considered expressly from a commercial perspective, for their use as screening tools to identify and optimise therapeutic constructs, rather than as research tools requiring minimal throughput. Commercial utility is discussed in terms of the sourcing and assembly of cell-based model components, likelihood of data outputs highly predictive of clinical performance, and the compromise between need for advanced 3D culture architectures and the incremental difficulty in assembling those structures cost-effectively for medium-throughput analysis. The relative merits of cell lines and primary human cells are discussed, the latter with respect to their potential physiological relevance when cultured under permissive conditions conferred by a biologically-rich micro-environment. Tools for assembly of such microenvironments are reviewed, and the practitioner's choices of commercial products enabling 3D cell culture are also critically evaluated, from the merits of cell aggregates and micro-tissues to the architectural attractions of recreating epithelial monolayers and multi-cell type reconstituted tissues. Additionally, pitfalls and practical challenges in co-assembly of cells and scaffolds/matrices are considered, with the intention of signposting routes to consistent, scalable production of 3D cell cultures capable of screening the nanomedical potential of NP-conjugated therapeutics.