ReviewPharmaceutics2025
Physiological Barriers to Nucleic Acid Therapeutics and Engineering Strategies for Lipid Nanoparticle Design, Optimization, and Clinical Translation.
Review in Pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed.
- Targeted delivery of mRNA to immune cells forDrug delivery · 2026Review
- Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.International journal of pharmaceutics: X · 2026Review
- Overcoming hepatic tropism: Precision engineering of lipid nanoparticles for extrahepatic RNA delivery.Materials today. Bio · 2026Review
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Rewriting the mRNA Delivery Map: Albumin Hitchhiking Lipid Nanoparticles for Safer and Smarter Nanomedicine.ACS materials Au · 2026Review
- Engineering Advanced Nanomedicine Against Depression: From Treatment Challenges to Delivery Strategies.Advanced healthcare materials · 2026Review
- Lipid-Based Delivery Systems for Therapeutic Glycoproteins: Current Advances, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Nanoparticulate and Hydrogel Vehicles for Stimuli-Responsive and Sustained Controlled Release of Active Pharmaceutical Ingredients.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.Journal of peptide science : an official publication of the European Peptide Society · 2026Article
- Mannose receptor-targeted MSC-derived exosomes as a high-affinity delivery platform for liver sinusoidal endothelial cells.Drug delivery and translational research · 2026Article
- Multifunctional nanotherapeutics for tumor microenvironment modulation in solid tumor therapy.Discover nano · 2026Review
- Review
- Barrier-Oriented Design of Next-Generation Polymeric Nanocarriers for Targeted Drug Delivery.Molecules (Basel, Switzerland) · 2026Review
- Functional Reclassification of Lipid-Based Drug Delivery Systems and Advances in Formulation Strategies and Manufacturing Challenges.AAPS PharmSciTech · 2026Review
- Investigation of Heterogeneity of Lipid Nanoparticles for Nucleic Acid Drug Delivery via Sucrose Gradient Density Centrifugation.International journal of molecular sciences · 2026Article
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Artificial Intelligence in the Design and Development of Nanoparticle Drug Delivery Systems: A Systematic Review.Advances in pharmacological and pharmaceutical sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid nanoparticles are a clinically validated platform for delivering nucleic acids, but performance is constrained by multiscale physiological barriers spanning circulation, vascular interfaces, extracellular matrices, cellular uptake, and intracellular trafficking. This review links composition-structure-function relationships for ionizable lipids, helper phospholipids, cholesterol, and PEG-lipids to systemic fate, endothelial access, endosomal escape, cytoplasmic stability, and nuclear transport. We outline strategies for tissue and cell targeting, including hepatocyte ligands, immune and tumor selectivity, and selective organ targeting through compositional tuning, together with approaches that modulate escape using pH-responsive chemistries or fusion-active peptides and polymers. We further examine immunomodulatory co-formulation, route and schedule effects on biodistribution and immune programming, and manufacturing and stability levers from microfluidic mixing to lyophilization. Across these themes, we weigh trade-offs between stealth and engagement, potency and tolerability, and potency and manufacturability, noting that only a small fraction of endosomes supports productive release and that protein corona variability and repeat dosing can reshape tropism and clearance. Convergence of standardized assays for true cytosolic delivery, biomarker-guided patient selection, and robust process controls will be required to extend LNP therapeutics beyond the liver while sustaining safety, access, and scale.
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.