Natural IgM dominates in vivo performance of liposomes

Prevalent deposition of plasma proteins on nano-surface alters the synthetic identity of liposomes in blood circulation. The key plasma protein(s) that can dominate in vivo fate of liposomes are of central importance for preclinical design and precise medication of liposome-based therapeutics. Herein, natural IgM, but not IgG, is identified to ubiquitously absorb on liposomal surface and takes the lead in complement activation of different species. The absorbed natural IgM, which negatively correlates with the in vivo performance of liposomes, becomes a potential indicator to guide the de novo design and optimization of liposomes. More importantly, the varying natural IgM levels in cancer patients may be one of the causal factors for clinical differences in response to liposome-based therapeutics. Clinical monitoring of the natural IgM level and its binding with liposomes becomes crucial to optimize the therapeutic regimen prior to the application of liposome-based therapeutics.