Nanomaterials in the blood must mitigate the immune response to have a prolonged vascular residency in vivo. The composition of the protein corona that forms at the nano-biointerface may be directing this, however, the possible correlation of corona composition with blood residency is currently unknown. Here' we report a panel of new soft single molecule polymer nanomaterials (SMPNs) with varying circulation times in mice (t ~ 22 to 65 h) and use proteomics to probe protein corona at the nano-biointerface to elucidate the mechanism of blood residency of nanomaterials. The composition of the protein opsonins on SMPNs is qualitatively and quantitatively dynamic with time in circulation. SMPNs that circulate longer are able to clear some of the initial surface-bound common opsonins, including immunoglobulins, complement, and coagulation proteins. This continuous remodelling of protein opsonins may be an important decisive step in directing elimination or residence of soft nanomaterials in vivo.
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http://dx.doi.org/10.1038/s41467-020-16772-x | DOI Listing |
Microbes Infect
January 2025
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address:
Leptospirosis is a zoonosis caused by spirochete Leptospira. Pathogenic leptospires evade the Complement System, enabling their survival upon contact with normal human serum in vitro. In a previous study, we demonstrated that proteases secreted by pathogenic leptospires cleave several Complement proteins, including C3 and the opsonins C3b and iC3b.
View Article and Find Full Text PDFBiomacromolecules
December 2024
Laboratory for Macromolecular and Organic Chemistry, Department of Chemical Sciences, University of Padova, Padova 35131, Italy.
Cyclic poly(2-methyl-2-oxazine) (-PMOZI) brush shells on Au nanoparticles (NPs) exhibit enhanced stealth properties toward serum and different cell lines compared to their linear PMOZI (-PMOZI) counterparts. While selectively recruiting immunoglobulins, -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.
View Article and Find Full Text PDFInt J Nanomedicine
December 2024
Department of Life Sciences, University of Trieste, Trieste, 34127, Italy.
Purpose: In the bloodstream, nanoparticles (NPs) interact with serum proteins to form the protein corona, which includes both opsonins, promoting NP recognition and elimination, and dysopsonins, which can inhibit opsonin activity. Albumin, the most abundant serum protein, is part of this corona and can act as a dysopsonin, potentially hiding NPs from the immune system. This study aims to investigate how a covalently bound layer of human serum albumin (HSA) on polymeric NPs affects the protein corona and their behavior in the immune system.
View Article and Find Full Text PDFEur J Clin Invest
December 2024
Department of Medicine, Masonic Cancer Center, University of Minnesota Medical Center, Minneapolis, Minnesota, USA.
Background: In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.
View Article and Find Full Text PDFAdv Mater
December 2024
Department of Systems Pharmacology and Translational Therapeutics, The Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd., 354 BRB II/III, Philadelphia, PA, 19104, USA.
Conjugation chemistries are a major enabling technology for the development of drug delivery systems, from antibody-drug conjugates to antibody-targeted lipid nanoparticles inspired by the success of the COVID-19 vaccine. However, here it is shown that for antibody-targeted nanoparticles, the most popular conjugation chemistries directly participate in the activation of the complement cascade of plasma proteins. Their activation of complement leads to large changes in the biodistribution of nanoparticles (up to 140-fold increased uptake into phagocytes of the lungs) and multiple toxicities, including a 50% drop in platelet count.
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