Performance of nanoparticles for biomedical applications: The in vitro/in vivo discrepancy

Nanomedicine has a great potential to revolutionize the therapeutic landscape. However, up-to-date results obtained from in vitro experiments predict the in vivo performance of nanoparticles weakly or not at all. There is a need for in vitro experiments that better resemble the in vivo reality. As a result, animal experiments can be reduced, and potent in vivo candidates will not be missed. It is important to gain a deeper knowledge about nanoparticle characteristics in physiological environment. In this context, the protein corona plays a crucial role. Its formation process including driving forces, kinetics, and influencing factors has to be explored in more detail. There exist different methods for the investigation of the protein corona and its impact on physico-chemical and biological properties of nanoparticles, which are compiled and critically reflected in this review article. The obtained information about the protein corona can be exploited to optimize nanoparticles for in vivo application. Still the translation from in vitro to in vivo remains challenging. Functional in vitro screening under physiological conditions such as in full serum, in 3D multicellular spheroids/organoids, or under flow conditions is recommended. Innovative in vivo screening using barcoded nanoparticles can simultaneously test more than hundred samples regarding biodistribution and functional delivery within a single mouse.

Automated summary

Nanomedicine has the potential to transform therapy, but current in vitro experiments have limited predictive power for in vivo performance. More realistic in vitro experiments are needed to reduce animal testing and identify promising candidates. Understanding the formation process of the protein corona, which plays a crucial role in nanoparticle characteristics, is important. Different methods for studying the protein corona and its impact on nanoparticles are reviewed. This information can be used to optimize nanoparticles for in vivo applications, although the transition from in vitro to in vivo remains challenging. Functional in vitro screening in physiological conditions and innovative in vivo screening using barcoded nanoparticles are recommended.