ArticleMolecules (Basel, Switzerland)2018
Understanding the Role of Anti-PEG Antibodies in the Complement Activation by Doxil in Vitro.
Article in Molecules (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 113 citations in OpenAlex.
- Therapeutic Targets, Pharmacological Mechanisms, and Delivery Strategies for Diabetic Peripheral Neuropathy.Drug design, development and therapy · 2026Review
- Charting new frontiers in nanoparticle immunotoxicity: A perspective on current, emerging, and future approaches.Biochemical and biophysical research communications · 2025Review
- The Therapeutic Potential of Photoimmunotherapy as a Safe, Effective and Non-Toxic Treatment Option for Superficial Triple Negative Breast Cancer.Cancer medicine · 2025Review
- Influence of the Saccharide Structure on Cargo Loading, Thermal Properties, and Lectin Binding of Amphiphilic Glycopolymer-Polylactic Acid Block Copolymer Nanoparticles.Bioconjugate chemistry · 2025Article
- Nanotechnology-Driven Drug Delivery Systems for Lung Cancer: Computational Advances and Clinical Perspectives.Thoracic cancer · 2025Review
- Implications of Anaphylaxis Following mRNA-LNP Vaccines: It Is Urgent to Eliminate PEG and Find Alternatives.Pharmaceutics · 2025Review
- Nucleic acid nanobiosystems for cancer theranostics: an overview of emerging trends and challenges.Nanomedicine (London, England) · 2025Review
- Better the devil you know than the devil you don't - PEG challenges in nanomedicine.Nature nanotechnology · 2025Article
- Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.Journal of pharmaceutical sciences · 2024Article
- Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts.ACS nano · 2024Article
- Biocompatible Glycopolymer-PLA Amphiphilic Hybrid Block Copolymers with Unique Self-Assembly, Uptake, and Degradation Properties.Biomacromolecules · 2024Article
- Nanocarrier design for pathogen-inspired innate immune agonist delivery.Trends in immunology · 2024Review
- Article
- Optimized Enzyme-Linked Immunosorbent Assay for Anti-PEG Antibody Detection in Healthy Donors and Patients Treated with PEGylated Liposomal Doxorubicin.Molecular pharmaceutics · 2024Article
- Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering.Nature communications · 2024Article
- Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin.Acta pharmacologica Sinica · 2024Article
- Absence of Anaphylactic Reactions to Injection of Hemoglobin Vesicles (Artificial Red Cells) to Rodents.ACS omega · 2024Article
- Detection of Pre-Existing Antibodies to Polyethylene Glycol and PEGylated Liposomes in Human Serum.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Interplay between Liposomes and IgM: Principles, Challenges, and Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Proteinoid Polymers and Nanocapsules for Cancer Diagnostics, Therapy and Theranostics: In Vitro and In Vivo Studies.Journal of functional biomaterials · 2023Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infusion reactions (IRs) are common immune-mediated side effects in patients treated with a variety of drug products, including, but not limited to, nanotechnology formulations. The mechanism of IRs is not fully understood. One of the best studied mechanisms of IRs to nanomedicines is the complement activation. However, it is largely unknown why some patients develop reactions to nanomedicines while others do not, and why some nanoparticles are more reactogenic than others. One of the theories is that the pre-existing anti-polyethylene glycol (PEG) antibodies initiate the complement activation and IRs in patients. In this study, we investigated this hypothesis in the case of PEGylated liposomal doxorubicin (Doxil), which, when used in a clinical setting, is known to induce IRs; referred to as complement activation-related pseudoallergy (CARPA) in sensitive individuals. We conducted the study in vitro using plasma derived from C57BL/6 mice and twenty human donor volunteers. We used mouse plasma to test a library of well-characterized mouse monoclonal antibodies with different specificity and affinity to PEG as it relates to the complement activation by Doxil. We determined the levels of pre-existing polyclonal antibodies that bind to PEG, methoxy-PEG, and PEGylated liposomes in human plasma, and we also assessed complement activation by Doxil and concentrations of complement inhibitory factors H and I in these human plasma specimens. The affinity, specificity, and other characteristics of the human polyclonal antibodies are not known at this time. Our data demonstrate that under in vitro conditions, some anti-PEG antibodies contribute to the complement activation by Doxil. Such contribution, however, needs to be considered in the context of other factors, including, but not limited to, antibody class, type, clonality, epitope specificity, affinity, and titer. In addition, our data contribute to the knowledge base used to understand and improve nanomedicine safety.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.