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Proteolytic activity of secreted proteases from pathogenic leptospires and effects on phagocytosis by murine macrophages.
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 PDFThe Topology of Poly(2-methyl-2-oxazine) Shells on Nanoparticles Determines Their Interaction with Serum and Uptake by Immune Cells.
Biomacromolecules
January 2025
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 PDFStealth-Engineered Albumin-Coated Nanoparticles for Targeted Therapy: Effective Drug Delivery and Tumor Suppression in Xenograft-Zebrafish Model.
Int 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 PDFA quantitative systems pharmacology (QSP) platform for preclinical to clinical translation of CRISPR-Cas therapy.
Front Pharmacol
September 2024
Center of Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, FL, United States.
Article Synopsis
- In-vivo CRISPR Cas genome editing therapy involves the use of lipid nanoparticles, mRNA, and single guide RNA, requiring prediction models due to limited data on their distribution in the body.
- A Quantitative Systems Pharmacology (QSP) model was developed to assess the pharmacokinetics and pharmacodynamics of CRISPR therapies, based on studies involving transthyretin amyloidosis and LDL-cholesterol reduction in mice and non-human primates transitioning to humans.
- The QSP model successfully described the biodistribution, key mechanisms post-injection, and the effect on serum TTR levels, demonstrating its potential in advancing the development of CRISPR-based therapies.
Murine C3 of the complement system affects infection by Leptospira interrogans.
Microbes Infect
September 2024
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address:
Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood.
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