Fabrication of active targeting lipid nanoparticles: Challenges and perspectives

Targeted drug and gene delivery is the key for precision therapy. Lipid nanoparticles as non-viral vectors have attracted extensive attentions in treating a variety of diseases, such as cancer, immune disease, cardiac diseases and pathogen infection. They exhibit low immunogenicity and low cytotoxicity, which make them as the most-commonly used vectors. More importantly, their surfaces could be functionalized, which provide a platform to improve targeting and pharmacokinetic/pharmacodynamic properties. Although there has been great success to synthesize lipid nanoparticles, it remains as a challenge to produce active targeting lipid nanoparticles especially with definable targetability, high quality and good translation reproducibility. This review focus on the techniques to fabricate active targeting lipid nanoparticles. We start with a brief introduction of targeting lipid nanoparticles, followed by a focused discussion of various preparation approaches including one-pot assembly and post-insertion functionalization. The methods, mechanism and representative examples are introduced, together with the comparison of their advantages and restrictions. Finally, challenges facing formulation screening and clinical translation are discussed.