Hypersensitivity to polymer-coated nanomedicines: mechanism, prediction and prevention

Gyula Tamas Gyula Tamas Fülöp

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Nanomedicines promise to deliver useful and valuable research tools and clinical applications. The connection of various nanomedicines to hypersensitivity reactions upon IV administration, called complement activation-related pseudoallergy (CARPA), will be introduced in these studies. Intravenous injection of a variety of nanomedicinal (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions, also known as infusion or anaphylactoid reactions. The molecular mechanism and severity of these allergy symptoms may alter from case to case and in many cases the major cause, or contributing factor is activation of the complement system. The clinical relevance of CARPA, a non-IgE-mediated allergy syndrome, lies in its unpredictability and occasionally lethal outcome. The research is planned to be centered around PEGylated liposomes and SPIONs (superparamagnetic iron oxide nanoparticles) as successful examples of marketed nanomaterials. These studies will mainly include in vivo pig models, one if not the best animal model for complement related pseudoallergy studies. Several parameters can be monitored during such in vivo experiments, including hemodynamic changes (heart rate, systemic arterial pressure, pulmonary arterial pressure, pCO2, SpO2), blood cell count analysis and thromboxane (TxB2) changes measured with ELISA. Indeed, the role of possible biomarkers as the previously mentioned TxB2, and the promising complement factor H (FH) are planned to be assessed in reviews. Another agent used in therapeutics that can induce C related HSRs similar to nanomedicines are monoclonal antibodies (mABs) with or without PEGylation. In conclusion, these planned experiments and reviews with diverse topics all aim to analyse the mechanics and background of complement related hypersensitivity reactions of polymer coated nanomedicines and biological molecules, trying to find possible preventive options or at least ways to reduce the level of these adverse events.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
  • Storm, G. , Supervisor
  • Szebeni, János, Co-Supervisor, External person
  • Metselaar, J.M., Supervisor
Award date11 Jan 2023
Place of PublicationEnschede
Print ISBNs978-90-365-5463-3
Publication statusPublished - 11 Jan 2023

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