Physiological relevance of in-vitro cell-nanoparticle interaction studies as a predictive tool in cancer nanomedicine research

Cell uptake study is a routine experiment used as a surrogate to predict in vivo response in cancer nanomedicine research. Cell culture conditions should be designed in such a way that it emulates 'real' physiological conditions and avoid artefacts. It is critical to dissect the steps involved in cellular uptake to understand the physical, chemical, and biological factors responsible for particle internalization. The two-dimensional model (2D) of cell culture is overly simplistic to mimic the complexity of cancer tissues that exist in vivo. It cannot simulate the critical tissue-specific properties like cell-cell interaction and cell-extracellular matrix (ECM) interaction and its influences on the temporal and spatial distribution of nanoparticles (NPs). The three dimensional model orga-nization of heterogenous cancer and normal cells with the ECM acts as a formidable barrier to NP penetration and cellular uptake. The three dimensional cell culture (3D) technology is a breakthrough in this direction that can mimic the barrier properties of the tumor microenvironment (TME). Herein, we discuss the physiological factors that should be considered to bridge the translational gap between in and vitro cell culture studies and in-vivo studies in cancer nanomedicine.

Automated summary

Cell uptake study is a routine experiment used to predict in vivo response in cancer nanomedicine research. It is critical to understand the factors responsible for particle internalization and the limitations of the two-dimensional cell culture model. The three-dimensional cell culture technology can better mimic the tumor microenvironment and improve the accuracy of in vitro studies.