ArticleAdvanced materials (Deerfield Beach, Fla.)2025
Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation.
Article in Advanced materials (Deerfield Beach, Fla.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Preparation of targeted lipid nanoparticles for precision nucleic acid delivery.Nature protocols · 2026Review
- Genetic Code Expansion Enables Oriented, Site-Specific Conjugation of DARPins to Lipid Nanoparticles for Selective mRNA Delivery to CD8International journal of molecular sciences · 2026Article
- Advances in Living Cell-Mediated Nanodrug Delivery Systems: Construction Strategies, Applications and Challenges.Pharmaceutics · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Antibody Conjugation Strategies for Ultrasound Microbubbles: A Review of Bioconjugation Chemistry and Clinical Translation.Ultrasound in medicine & biology · 2026Review
- Decoupling Physisorption from Chemisorption in Clickable Lipid Nanoparticles.ACS nanoscience Au · 2026Article
- DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Spontaneous Non-Catalyzed Molecular Reactions and Interactions in the Human Body: Biomedical Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Recent advances in the application of polymeric nanoparticles to the pulmonary delivery of mRNA.Nanomedicine (London, England) · 2026Review
- Lipid nanoparticles for bone marrow-targeted RNA therapeutics.Journal of nanobiotechnology · 2026Review
- The antifibrotic effects of a click chemistry-based albumin nanocomplex in an idiopathic pulmonary fibrosis model.Journal of nanobiotechnology · 2026Article
- Article
- Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.Frontiers in chemistry · 2026Review
- Nanotoxicity of Porous Silica Nanoparticles: Physicochemical Properties and Mechanistic Cellular Endpoints.Nanomaterials (Basel, Switzerland) · 2025Review
- Antibody-conjugated polymer nanoparticles for brain cancer.Drug delivery and translational research · 2025Review
- Broad-spectrum vaccines against various and evolving viruses: from antigen design to nanoparticle delivery.Journal of virology · 2025Review
- Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage.Journal of neuroinflammation · 2025Article
- Development of Novel Neratinib and Docetaxel Core-Loaded and Trastuzumab Surface-Conjugated Nanoparticle for Treatment of HER-2 Positive Breast Cancer.Pharmaceutics · 2025Article
- Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
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. It is founded that the mechanism of complement activation varies dramatically between different conjugation chemistries. Dibenzocyclooctyne, a commonly used click-chemistry, caused aggregation of conjugated antibodies, but only on the surface of nanoparticles (not in bulk solution). By contrast, thiol-maleimide chemistry do not activate complement via its effects on antibodies, but rather because free maleimide bonded to albumin in plasma, and clustered albumin is then attacked by complement. Using these mechanistic insights, solutions are engineered that reduced the activation of complement for each class of conjugation chemistry. These results highlight that while conjugation chemistry is essential for the future of nanomedicine, it is not innocuous and must be designed with opsonins like complement in mind.
Indexed as
Identifiers
What OpenQuestion holds
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.