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Volume 4
Nano Research & Applications
ISSN: 2471-9838
Page 78
JOINT EVENT
August 16-18, 2018 | Dublin, Ireland
&
12
th
Edition of International Conference on
Nanopharmaceutics and Advanced Drug Delivery
25
th
Nano Congress for
Future Advancements
Nano Congress 2018
&
Nano Drug Delivery 2018
August 16-18, 2018
Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-015
Major role of complement activation compared to protein corona composition in the capture of stealth-
NP by phagocytes: Inter-individual and inter-species variability
Emanuele Papini
University of Padua, Italy
U
nderstanding the functional properties of a new nano-biointerface created by host proteins adsorbed on nanoparticles
(NPs), or nanoparticle protein corona, masking the pristine nanomaterial is considered by many the obliged “golden
gate” to their clinical application. Rapid clearance by the reticular endothelial system (RES) phagocytes is a major obstacles for
nanotheranostics developments and the protein corona may indeed favor or hamper such process. However, also complement
activation may increase RES clearance and contribute to proinflammatory and infusion-related reactions. Poly(ethylene glycol)
(PEG) NPs coatings, used to minimize protein interaction and RES clearance (stealthing effect) may trigger complement,
thereby improving phagocytes capture and infusion-related reactions. Poly(2-mehyl-2-oxazoline) (PMOXA) and poly(2-
ethyl-2-oxazoline) (PETOXA) have been proposed as alternative polymer for NP surface modification, due to their improved
chemical/physicochemical features compared with PEG. We characterized PEG, PMOXA and PETOXA performance and
evaluated the relative importance of protein corona formation vs complement activation. Specifically, we tested the efficacy of
human monocytes, macrophages and PMNGs to capture 100 nm ORMOSIL-NPs, coated with above indicated polymers, in
human serum. PEG and, especially, PMOXA and PETOXA coatings increased complement activation and opsonine-mediated
NP capture by phagocytes compared to naked NPs. The surface-dependent composition diversities of the serum protein
corona formed on the different NP formulations were poorly relevant since, in the absence of complement, a similar stealth
effect was invariably measured. Tests using sera from different human subjects, mice and pigs showed crucial subject- and
species-dependent differences. We conclude that complement cascade activation is a major factor negatively affecting the
stealthing efficacy of PEG, PMOXA and PETOXA coats on NPs. Species-specific diversities of such mechanisms in pre-clinical
models, e.g. the murine one, may lead to wrong NP efficacy extrapolations to the human contest. This demands the search for
complement-inert nanoparticle coatings.
emanuele.papini@unipd.it