The Topology of Poly(2-methyl-2-oxazine) Shells on Nanoparticles Determines Their Interaction with Serum and Uptake by Immune Cells
Cyclic poly(2-methyl-2-oxazine) (<i>c</i>-PMOZI) brush shells on Au nanoparticles (NPs) exhibit enhanced stealth properties toward serum and different cell lines compared to their linear PMOZI (<i>l</i>-PMOZI) counterparts. While selectively recruiting immunoglobulins, <i>c</i>-PMOZI shells reduce overall human serum (HS) protein binding and alter the processing of complement factor 3 (C3) compared to chemically identical linear shells. Polymer cyclization significantly decreases NP uptake by nonphagocytic cells and macrophages in both complement-deficient fetal bovine serum (FBS) and complement-expressing HS, indicating ineffective functional opsonization. Even in serum-free media, <i>c</i>-PMOZI-coated NPs show reduced internalization by macrophages compared to <i>l</i>-PMOZI-coated NPs, suggesting lower opsonin-independent cell surface affinity. This study demonstrates that cyclic PMOZI suppresses interactions of NPs with proteins and cells, highlighting how control over chain topology expands the polymer chemistry toolbox for modulating the behavior of core-shell NPs within physiological environments.
Authors
- Emanuele Papini (ORCID: https://orcid.org/0000-0001-6033-4473)
- Yashoda Chandorkar (ORCID: https://orcid.org/0000-0001-8263-7002)
- Edmondo Maria Benetti (ORCID: https://orcid.org/0000-0002-5657-5714)
- Cinzia Franchin (ORCID: https://orcid.org/0000-0001-9223-117X)
- Regina Tavano (ORCID: https://orcid.org/0000-0002-0699-1859)
- Matteo Romio (ORCID: https://orcid.org/0000-0002-7119-4258)
- Denis Badocco (ORCID: https://orcid.org/0000-0001-6270-7966)
- Massimo Morbidelli (ORCID: https://orcid.org/0000-0002-0112-414X)
- Paolo Pastore (ORCID: https://orcid.org/0000-0003-1448-0175)
- Giorgio Arrigoni (ORCID: https://orcid.org/0000-0002-4103-2733)
- Richard Hoogenboom (ORCID: https://orcid.org/0000-0001-7398-2058)
- Cordula Hirsch (ORCID: https://orcid.org/0000-0001-5689-4291)
- Lucca Trachsel (ORCID: https://orcid.org/0000-0002-4342-1003)
- Francesca Lorandi (ORCID: https://orcid.org/0000-0001-5253-8468)
- Alexander Gogos (ORCID: https://orcid.org/0000-0001-6233-512X)
- Barbora Kolrosova
Institutions
- University of Padua (IT)
- Ghent University (BE)
- Institute of Macromolecular Chemistry (UA)
- Swiss Federal Laboratories for Materials Science and Technology (CH)
- Carnegie Mellon University (US)
Publication Details
- Journal
- Biomacromolecules
- Published
- 2024-12-26
- DOI
- https://doi.org/10.1021/acs.biomac.4c01340
- Citations
- 7
- Primary Topic
- Synthesis and Characterization of Heterocyclic Compounds
- Type
- article
- Field-Weighted Citation Impact
- 1.75
Funders
- European Commission
- Horizon 2020 Framework Programme