Lipid nanoparticles (LNPs) made the jump from scientific journals to public awareness in a matter of months as the mechanism delivering mRNA vaccines into millions of people’s arms around the world.
While this delivery system enabled protection levels beyond any initial expectation, LNPs are only one means of introducing therapeutics via nanomaterials into the blood stream. Nanomedicine’s potential is tremendous, but unlocking its possibilities requires significant work to identify and mitigate any potential toxicity.
The interaction between the immune system and nanomaterials is the focus of an important study led by Centre for Blood Research investigator Jayachandran Kizhakkedathu, with UBC and international collaborators published in Nature Communications.
The researchers developed a new vehicle –mega polyglycerols–which features an extraordinarily long half-life–up to 65 hours in the circulatory system in mice—in order to observe the potential pathways that can be utilized by nanomaterials. They then used proteomics to study what happened to the nanoparticles while they were circulating.
When a foreign material is introduced into a living organism, proteins immediately form a corona around the intruder. The composition of those proteins has been thought to dictate the fate of materials in the blood. The researchers found this was a highly dynamic process inside the body, making the discovery that some nanoparticles that ditch their opsonizing proteins—which tag foreign entities for elimination by macrophages—can stay in circulation, while others get cleared by the immune system.
Understanding this phenomenon will enable researchers to develop novel nanomedicines with improved capacity for circulation and minimal toxicity for a range of applications. Many questions remain about corona formation on nanomaterials, such as which proteins contribute to longer circulation and which contribute to rapid clearance.
The Kizhakkedathu Lab is working on determining how protein binding in animal models differs between tissue-targeted vs systemic nanotherapeutics. They are also exploring how different health conditions affect dynamic protein corona formation, to gain additional insights on immune recognition of different nanomedicines.
Read the paper
Abbina, S, Takeuchi LE, Anilkumar, P. Yu, K, Rogalski, JC, Shenoi, RA, Constaninescu, I, and Kizhakkedathu, JN. Blood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface. Nat Commun 11, 3048 (2020). https://doi.org/10.1038/s41467-020-16772-x