Organoids: A new approach in toxicity testing of nanotherapeutics

Nanotechnology has revolutionized diverse fields, which include agriculture, the consumer market, medicine, and other fields. Widespread use of nanotechnology-based products has led to increased prevalence of these novel formulations in the environment, which has raised concerns regarding their deleterious effects. The application of nanotechnology-based formulations into clinical use is hampered by the lack of the availability of effective in vitro systems, which could accurately assess their in vivo toxic effects. A plethora of studies has shown the hazardous effects of nanoparticle-based formulations in two-dimensional in vitro cell cultures and animal models. These have some associated disadvantages when used for the evaluation of nano-toxicity. Organoid technology fills the space between existing two-dimensional cell line culture and in vivo models. The uniqueness of organoids over other systems for evaluating toxicity caused by nano-drug formulation includes them being a co-culture of diverse cell types, dynamic flow within them that simulates the actual flow of nanoparticles within biological systems, extensive cell-cell, cell-matrix interactions, and a tissue-like morphology. Thus, it mimics the actual tissue microenvironment and, subsequently, provides an opportunity to study drug metabolism and toxico-dynamics of nanotechnology-based novel formulations. The use of organoids in the evaluation of nano-drug toxicity is in its infancy. A limited number of studies conducted so far have shown good predictive value and efficiently significant data correlation with the clinical trials. In this review, we attempt to introduce organoids of the liver, lungs, brain, kidney intestine, and potential applications to evaluate toxicity caused by nanoparticles.