ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Cellular Uptake of Phase-Separating Peptide Coacervates.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed.
- Functionalized Coacervates for Cancer Therapy: Advances and Prospects in Phase-Separation-Based Intelligent Drug Delivery.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Oligopeptides/DNA Coacervate Droplets as Macromolecular Delivery Microcarriers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reversible Nucleolar Complex Coacervation by Short Cationic Peptides.Journal of the American Chemical Society · 2026Article
- Coacervate-Mediated Lysosome-Targeting Antibody Delivery for Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding the tactics for coacervate pedestrian crossing the phospholipid membrane.Chemical science · 2026Review
- Tuning mechanical softness as a design principle in drug delivery: A biomechanical perspective.Acta pharmaceutica Sinica. B · 2026Review
- Glycine Composition and Ion Valency Tune Phase Behavior and Drug Encapsulation in Designer Peptide Condensates.ACS applied materials & interfaces · 2026Article
- Delivery of peptide coacervates to form stable interaction hubs in cells.Nature communications · 2026Article
- Phase-Separated Coacervates of Low-Molecular-Weight Compounds for Cytosolic Delivery and Disease Treatment.JACS Au · 2025Review
- Intracellular Transport of Monomeric Peptides, (Poly)Peptide-Based Coacervates and Fibrils: Mechanisms and Prospects for Drug Delivery.International journal of molecular sciences · 2025Review
- Article
- Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulating Enzyme Activity via Microaggregates Mediated by Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Peptide coacervates as intracellular delivery vehicles for synergistic cancer photothermal- and chemo-therapies.APL bioengineering · 2025Article
- Polymeric and Polymer-Functionalized Drug Delivery Vectors: From Molecular Architecture and Elasticity to Cellular Uptake.Polymers · 2025Review
- Next-generation materials for nucleic acid delivery.Nature reviews. Materials · 2025Article
- Engineered Peptide Coacervates Enable Efficient Intracellular Delivery of the MYC Inhibitor omoMYC.Molecular pharmaceutics · 2025Article
- Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo.bioRxiv : the preprint server for biology · 2025Article
- Peptides: potential delivery systems for mRNA.RSC chemical biology · 2025Review
- Converging frontiers in biomolecular condensate and synthetic cell research.npj biomedical innovations · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Peptide coacervates self-assembling via liquid-liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non-cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, we identify the key steps by which droplets enter the cell. We find that the uptake follows a non-canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia-like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge- and cholesterol-dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors - interfering with actin and tubulin polymerization - confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non-specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate-based strategies for intracellular delivery of macromolecular therapeutics.
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