Impact of physicochemical properties on biological effects of lipid nanoparticles: Are they completely safe

Lipid nanoparticles (LNPs) are promising materials and human-use approved excipients, with manifold applications in biomedicine. Researchers have tended to focus on improving the pharmacological efficiency and organ targeting of LNPs, while paid relatively less attention to the negative aspects created by their specific physicochemical properties. Here, we discuss the impacts of LNPs' physicochemical properties (size, surface hydrophobicity, surface charge, surface modification and lipid composition) on the adsorption-transportation-distribution-clearance processes and bio-nano interactions. In addition, since there is a lack of review emphasizing on toxicological profiles of LNPs, this review outlined immunogenicity, inflammation, hemolytic toxicity, cytotoxicity and genotoxicity induced by LNPs and the underlying mechanisms, with the aim to understand the properties that underlie the biological effects of these materials. This provides a basic strategy that increased efficacy of medical application with minimized side-effects can be achieved by modulating the physicochemical properties of LNPs. Therefore, addressing the effects of physicochemical properties on toxicity induced by LNPs is critical for understanding their environmental and health risks and will help clear the way for LNPs-based drugs to eventually fulfill their promise as a highly effective therapeutic agents for diverse diseases in clinic.