Influence of charge on hemocompatibility and immunoreactivity of polymeric nanoparticles

Liyu Chen, Joshua J. Glass, Robert De Rose, Claudia Sperling, Stephen J. Kent, Zachary H. Houston, Nicholas L. Fletcher, Barbara E. Rolfe, Kristofer J. Thurecht

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

The 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, chargevaried 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.

Original languageEnglish
Pages (from-to)756-767
Number of pages12
JournalACS Applied Bio Materials
Volume1
Issue number3
DOIs
Publication statusPublished - Sep 2018

Keywords

  • Branched polymer
  • Hemocompatibility
  • Immune response
  • Nanomaterials
  • Nanomedicines

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