Many PEGylated nanoparticles activate the complement system, which is an integral component of innate immunity. This is of concern as uncontrolled complement activation is potentially detrimental and contributes to disease pathogenesis. Here, it is demonstrated that, in contrast to carboxyPEG2000- stabilized poly(lactic-co-glycolic acid) nanoparticles, surface camouflaging with appropriate combinations and proportions of carboxyPEG2000 and methoxyPEG550 can largely suppress nanoparticle- mediated complement activation through the lectin pathway. This is attributed to the ability of the short, rigid methoxyPEG550 chains to laterally compress carboxyPEG2000 molecules to become more stretched and assume an extended, random coil configuration. As supported by coarse-grained molecular dynamics simulations, these conformational attributes minimize statistical protein binding/intercalation, thereby affecting sequential dynamic processes in complement convertase assembly. Furthermore, PEG pairing has no additional effect on nanoparticle longevity in the blood and macrophage uptake. PEG pairing significantly overcomes nanoparticle-mediated complement activation without the need for surface functionalization with complement inhibitors.
Bibliographical noteFunding Information:
This project was partially supported by the European Research Council, under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 616695, by the Italian Association for Cancer Research (AIRC) under the individual investigator Grant No. 17664, and by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 754490 - MINDED. S.M.M. and L-P.W. further acknowledge financial support by International Science and Technology Cooperation Project of HuangPu (No. 2018GH15), Guangzhou City, with RiboBio Co. Ltd., China.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics
- Mechanical Engineering