ArticleThe AAPS journal2021
Development of Lipidoid Nanoparticles for siRNA Delivery to Neural Cells.
Article in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed.
- Engineering polymeric RNA scaffolds as programmable combinatorial innate immune agonists.Nucleic acids research · 2026Article
- Macrophage polarization in inflammatory regulation: molecular mechanisms, therapeutic targets, and translational challenges.Cellular and molecular life sciences : CMLS · 2026Review
- Targeted Gene Delivery to MCF-7 Cells via Polyspermine-PEG-Glucose/DNA Nanoparticles: Preparation and Characterization.Molecular biotechnology · 2026Article
- Review
- Systemic mRNA-LNP administration in fetuses improves survival in a mouse model of spinal muscular atrophy.Molecular therapy. Methods & clinical development · 2025Article
- Oral delivery of stabilized lipid nanoparticles for nucleic acid therapeutics.Drug delivery and translational research · 2025Article
- Brain neurons internalise polymeric micron-sized capsules: Insights fromMaterials today. Bio · 2025Article
- Bioinspired Extracellular Vesicles for Enhanced Delivery of siRNA to Tumors.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Advancing Small Nucleic Acid Drug Delivery: From Stability Challenges to Novel Therapeutic Applications.Current drug delivery · 2025Review
- Efficient mRNA Delivery In Vitro and In Vivo Using a Polycharged Biodegradable Nanomaterial.International journal of molecular sciences · 2024Article
- Diversity of extracellular vesicles derived from calli, cell culture and apoplastic fluid of tobacco.Scientific reports · 2024Article
- Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery.International journal of pharmaceutics: X · 2024Review
- Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.Purinergic signalling · 2024Article
- Application of Nanotechnology and Phytochemicals in Anticancer Therapy.Pharmaceutics · 2024Review
- Review on Electrospray Nanoparticles for Drug Delivery: Exploring Applications.Polymers for advanced technologies · 2024Article
- Ionic liquid-coated lipid nanoparticles increase siRNA uptake into CNS targets.Nanoscale advances · 2024Article
- Nanoparticle-Facilitated Therapy: Advancing Tools in Peripheral Nerve Regeneration.International journal of nanomedicine · 2024Review
- Oral delivery of RNAi for cancer therapy.Cancer metastasis reviews · 2023Review
- Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy.Pharmaceutics · 2023Review
- Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipidoid nanoparticles (LNPs) are the delivery platform in Onpattro, the first FDA-approved siRNA drug. LNPs are also the carriers in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While these applications have demonstrated that LNPs effectively deliver nucleic acids to hepatic and muscle cells, it is unclear if LNPs could be used for delivery of siRNA to neural cells, which are notoriously challenging delivery targets. Therefore, the purpose of this study was to determine if LNPs could efficiently deliver siRNA to neurons. Because of their potential delivery utility in either applications for the central nervous system and the peripheral nervous system, we used both cortical neurons and sensory neurons. We prepared siRNA-LNPs using C12-200, a benchmark ionizable cationic lipidoid along with helper lipids. We demonstrated using dynamic light scattering that the inclusion of both siRNA and PEG-lipid provided a stabilizing effect to the LNP particle diameters and polydispersity indices by minimizing aggregation. We found that siRNA-LNPs were safely tolerated by primary dorsal root ganglion neurons. Flow cytometry analysis revealed that Cy5 siRNA delivered via LNPs into rat primary cortical neurons showed uptake levels similar to Lipofectamine RNAiMAX-the gold standard commercial transfection agent. However, LNPs demonstrated a superior safety profile, whereas the Lipofectamine-mediated uptake was concomitant with significant toxicity. Fluorescence microscopy demonstrated a time-dependent increase in the uptake of LNP-delivered Cy5 siRNA in a human cortical neuron cell line. Overall, our results suggest that LNPs are a viable platform that can be optimized for delivery of therapeutic siRNAs to neural cells.
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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.