ArticleProceedings of the National Academy of Sciences of the United States of America2024
Electrostatic adsorption of polyanions onto lipid nanoparticles controls uptake, trafficking, and transfection of RNA and DNA therapies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Modeling lung adenocarcinoma using layer-by-layer nanoparticles mitigates innate immune cell activation.bioRxiv : the preprint server for biology · 2026Article
- Engineering nanoparticle surface chemistry for antigen-presenting cell targeting improves specificity and safety of TLR3 agonist cancer immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Delivery of Monomethyl Auristatin E Using Ionizable Lipid Nanoparticles for B‑Cell Acute Lymphoblastic Leukemia Treatment.ACS omega · 2026Article
- A rapid and reliable strategy for identification of LNP and protein corona in vitro and in vivo.International journal of pharmaceutics: X · 2026Article
- mRNA Delivery by Lipoamino Fatty Acid-Peptide Polyplexes in Different Lung Cell Models and Lungs.Polymers · 2026Article
- Tetrahedral framework nucleic acids as a promising vehicle for small molecule drugs of traditional Chinese medicine: application to disease prevention and treatment.Journal of nanobiotechnology · 2026Review
- Subcellular nanoparticle trafficking investigated with label-free, live cell imaging.Nanoscale horizons · 2026Article
- From RNA to DNA: How Cargo Identity Reprograms Lipid Nanoparticle Architecture and Function.Advanced healthcare materials · 2026Review
- Evaluation of anionic polymer-coated siRNA lipoplexes prepared using a modified ethanol injection method.Biomedical reports · 2026Article
- Polyanion Chemistry Engineers Ternary RNA Nanoparticle Structure/Function from the Inside-Out.ACS nano · 2026Article
- KNTC1 initiates a KNTC1/E2F8/MYC positive feedback loop to facilitate tumorigenesis and enhance chemoresistance in bladder cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Delivery of small interfering RNA through lyophilized natural lipid nanoparticles: effects of natural lipid selection.Pharmaceutical biology · 2025Article
- Impact of Nanoparticle Stiffness on Endosomal Escape and Signaling Pathways in Cytosolic Delivery.Advanced healthcare materials · 2025Article
- Emerging lipid nanoparticle systems capable of efficient intramuscular RNA delivery.Nanomedicine (London, England) · 2025Review
- Advancing engineering design strategies for targeted cancer nanomedicine.Nature reviews. Cancer · 2025Review
- Automated and parallelized microfluidic generation of large and precisely-defined lipid nanoparticle libraries.bioRxiv : the preprint server for biology · 2025Article
- Circular RNA circBNC2 inhibits tumorigenesis by modulating ferroptosis and acts as a nanotherapeutic target in prostate cancer.Molecular cancer · 2025Article
- Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus.Advanced healthcare materials · 2025Article
- Nanoparticle Targeting Strategies for Lipid and Polymer-Based Gene Delivery to Immune Cells In Vivo.Small science · 2024Article
- Interaction of γ-Polyglutamic Acid/Polyethyleneimine/Plasmid DNA Ternary Complexes with Serum Components Plays a Crucial Role in Transfection in Mice.Pharmaceutics · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Rapid advances in nucleic acid therapies highlight the immense therapeutic potential of genetic therapeutics. Lipid nanoparticles (LNPs) are highly potent nonviral transfection agents that can encapsulate and deliver various nucleic acid therapeutics, including but not limited to messenger RNA (mRNA), silencing RNA (siRNA), and plasmid DNA (pDNA). However, a major challenge of targeted LNP-mediated systemic delivery is the nanoparticles' nonspecific uptake by the liver and the mononuclear phagocytic system, due partly to the adsorption of endogenous serum proteins onto LNP surfaces. Tunable LNP surface chemistries may enable efficacious delivery across a range of organs and cell types. Here, we describe a method to electrostatically adsorb bioactive polyelectrolytes onto LNPs to create layered LNPs (LLNPs). LNP cores varying in nucleic acid cargo and component lipids were stably layered with four biologically relevant polyanions: hyaluronate (HA), poly-L-aspartate (PLD), poly-L-glutamate (PLE), and polyacrylate (PAA). We further investigated the impact of the four surface polyanions on the transfection and uptake of mRNA- and pDNA-loaded LNPs in cell cultures. PLD- and PLE-LLNPs increased mRNA transfection twofold over unlayered LNPs in immune cells. HA-LLNPs increased pDNA transfection rates by more than twofold in epithelial and immune cells. In a healthy C57BL/6 murine model, PLE- and HA-LLNPs increased transfection by 1.8-fold to 2.5-fold over unlayered LNPs in the liver and spleen. These results suggest that LbL assembly is a generalizable, highly tunable platform to modify the targeting specificity, stability, and transfection efficacy of LNPs, as well as incorporate other charged targeting and therapeutic molecules into these systems.
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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.