ArticleAngewandte Chemie (International ed. in English)2026
Enhanced-mRNA Delivery Using Ultrasound-Delivered Anchors for Bioorthogonal Ligation.
Article in Angewandte Chemie (International ed. in English), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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.
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Who cites it
3 citing papers in PubMed.
- Programmable nanomedicine via bioorthogonal molecular engineering.Nano convergence · 2026Review
- Functionalized Lipid Nanoparticles for Targeted RNA Delivery in Immune and Inflammatory Diseases.Biomedicines · 2026Review
- PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation.Beilstein journal of nanotechnology · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Therapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound (FUS) to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with trans-cyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), producing ACRA-TCO and ACRA-mTz. ACRA derivatives were screened for cellular activity, yielding functionalized DOPE-PEG (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)) derivatives outperforming those containing saturated lipid or branched PEG. Nanobubbles encapsulating ultrasound-responsive gas delivered ACRA-TCO to targeted cells and tissues using FUS. This pre-targeting promoted the subsequent delivery of mRNA-LNP functionalized with companion ACRA-mTz. Ultrasound pre-targeting enhanced the accumulation of mTz-functionalized nanoparticles in cell cultures and mice by 75% and up to 3.6-fold, respectively, and increased gene expression using mRNA-LNP in vivo. Microbubbles loaded with ACRA roughly doubled mRNA delivery to the heart, while ultrasound alone did not. Taken together, this report presents a modular, ultrasound-enabled strategy for enhancing nucleic acid delivery in targeted tissues.
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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 Socratic graph.