Journal
BIOMATERIALS
Volume 30, Issue 12, Pages 2231-2240Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.01.005
Keywords
Lipid-polymer hybrid nanoparticles; Surface functional groups; Complement system activation; Human plasma protein binding; Coagulation system
Funding
- National Institutes of Health [CA719349, EB003647]
- David Koch-Prostate Cancer Foundation Award
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Here we report the immunological characterization of lipid-polymer hybrid nanoparticles (NPs) and propose a method to control the levels of complement activation induced by these NPs. This method consists of the highly specific modification of the NP surface with methoxyl, carboxyl, and amine groups. Hybrid NPs with methoxyl surface groups induced the lowest complement activation, whereas the NPs with amine surface groups induced the highest activation. All possible combinations among carboxyl, amine, and methoxyl groups also activated the complement system to a certain extent. All types of NPs activated the complement system primarily via the alternative pathway rather than the lectin pathway. The classical pathway was activated to a very small extent by the NPs with carboxyl and amine surface groups. Human serum and plasma protein binding studies showed that these NPs had different protein binding patterns. Studies of both complement activation and coagulation activation suggested that NPs with methoxyl surface groups might be an ideal candidate for drug delivery applications, since they are not likely to cause any immunological adverse reaction in the human body. Published by Elsevier Ltd.
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