mt8b00220_si_001.pdf (2.99 MB)
Influence of Charge on Hemocompatibility and Immunoreactivity of Polymeric Nanoparticles
journal contribution
posted on 2018-09-05, 15:03 authored by Liyu Chen, Joshua J. Glass, Robert De Rose, Claudia Sperling, Stephen J. Kent, Zachary H. Houston, Nicholas L. Fletcher, Barbara E. Rolfe, Kristofer J. ThurechtThe benefits of nanomedicine
may be restricted by hemocompatibility
and immunoreactivity problems arising from administration of exogenous
materials into the bloodstream. To understand how surface charge influences
the interaction of polymeric nanoparticles with blood components,
we synthesized three well-defined, charge-varied hyperbranched polymers
(HBPs) of similar size and analyzed both hemocompatibility and immunoreactivity
of these methacrylate-based HBPs ex vivo using primary human blood
cell assays and image analyses following intravenous injection into
mice. The results show that, regardless of charge, endotoxin-free
HBPs had minimal effects on coagulation, platelet, complement, or
T cell activation. However, high concentrations (100 μg mL–1) of cationic HBPs led to significant dendritic cell
activation, suggesting the potential application of these nanoparticles
as vaccine adjuvants to aid efficient antigen presentation. Biodistribution
studies showed that intravenously administered charge-neutral HBPs
had a longer retention time in the circulation than cationic or anionic
HBPs; whereas these neutral HBPs were eventually cleared in the urine,
charged HBPs mainly accumulated in liver and spleen. Overall, these
results demonstrate that, regardless of surface charge, HBPs display
a high level of hemocompatibility. In contrast, immunoreactivity and
biodistribution are significantly influenced by charge. Manipulation
of surface charge may thus be a useful method by which nanomaterials
such as HBPs can be tailored to different clinical applications.