Reality Check for Nanomaterial-Mediated Therapy with 3D Biomimetic Culture Systems

The recent progresses in tissue engineering and nanomaterial-based therapeutics/theranostics have led to the ever increasing utilization of 3D in vitro experimental models as the bona fide culture systems to evaluate the therapeutic/theranostic effects of nanomedicine. Compared to the use of conventional 2D culture platforms, 3D biomimetic cultures offer unmatched advantages as relevant physiological and pathological elements can be incorporated to allow better characterization of the engineered bio-nanomaterials in the targeted tissue-specific microenvironment. In this Feature Article, the current state-of-the-art 3D in vitro models that have been developed for the evaluation of biosafety and efficacy of nano- therapeutics/theranostics targeting the colon, blood–brain barrier (BBB), lungs, skin tumor models to bridge the nanomedicine bench to pre-clinical ravine are reviewed. Furthermore, the critical physicochemical parameters of the bio-nanomaterials that govern its transport and biodistribution in a complex 3D microenvironment will be highlighted. The major challenges and future prospects of evaluating nanomedicine in the third dimension will also be discussed.