ArticleACS nanoscience Au2026
Decoupling Physisorption from Chemisorption in Clickable Lipid Nanoparticles.
Article in ACS nanoscience Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
16 authors.
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Abstract
Antibody conjugation is essential for targeted lipid nanoparticle (LNP) delivery, but here we show that click-chemistry produces artifacts that confound accurate measurement of covalent antibody-LNP bonding. We demonstrate that hydrophobic interactions between the most common click alkyne linker, dibenzocyclooctyne (DBCO), and the inherently hydrophobic LNP surface drive extensive nonspecific antibody physisorption, even in the absence of LNP azide groups. This physisorption yields artificially high apparent conjugation efficiencies measured by chromatographic methods. In contrast, less hydrophobic liposomes exhibit azide-dependent conjugation, highlighting a consequence of nanoparticle surface chemistry. Plasma incubation rapidly displaces physisorbed antibodies from LNPs, confirming their weak, noncovalent association, whereas covalently bound antibodies remain attached and enable effective
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