ArticleCellular and molecular bioengineering2016
Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes.
Article in Cellular and molecular bioengineering, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Nanomedicine-based strategies for the treatment of vein graft disease.Nature reviews. Cardiology · 2025Review
- Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty.Biomaterials · 2025Article
- Core polymer optimization of ternary siRNA nanoparticles enhances in vivo safety, pharmacokinetics, and tumor gene silencing.Biomaterials · 2023Article
- Elucidating the Therapeutic Potential of Cell-Penetrating Peptides in Human Tenon Fibroblast Cells.ACS omega · 2022Article
- High-throughput and high-content bioassay enables tuning of polyester nanoparticles for cellular uptake, endosomal escape, and systemic in vivo delivery of mRNA.Science advances · 2022Article
- Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch.JCI insight · 2021Article
- Intracellular galectins sense cytosolically exposed glycans as danger and mediate cellular responses.Journal of biomedical science · 2021Review
- Nanoscopy for endosomal escape quantification.Nanoscale advances · 2021Review
- pH-Responsive Amphiphilic Carboxylate Polymers: Design and Potential for Endosomal Escape.Frontiers in chemistry · 2021Review
- Modifying Cell Membranes with Anionic Polymer Amphiphiles Potentiates Intracellular Delivery of Cationic Peptides.ACS applied materials & interfaces · 2020Article
- Genetically Encoded Split-Luciferase Biosensors to Measure Endosome Disruption Rapidly in Live Cells.ACS sensors · 2020Article
- Endosomolytic and Tumor-Penetrating Mesoporous Silica Nanoparticles for siRNA/miRNA Combination Cancer Therapy.ACS applied materials & interfaces · 2020Article
- An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles.Nature communications · 2019Article
- Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy.Nature nanotechnology · 2019Article
- Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability.ACS nano · 2019Article
- HOPS-dependent endosomal fusion required for efficient cytosolic delivery of therapeutic peptides and small proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Intranasal MMI-0100 Attenuates AβFrontiers in immunology · 2019Article
- Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines.Biomaterials · 2018Article
- Excipients for the lyoprotection of MAPKAP kinase 2 inhibitory peptide nano-polyplexes.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival.Cancer research · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Electrostatic complexation of a cationic MAPKAP kinase 2 inhibitory (MK2i) peptide with the anionic, pH-responsive polymer poly(propylacrylic acid) (PPAA) yields MK2i nano-polyplexes (MK2i-NPs) that significantly increase peptide uptake and intracellular retention. This study focused on elucidating the mechanism of MK2i-NP cellular uptake and intracellular trafficking in vascular smooth muscle cells. Small molecule inhibition of various endocytic pathways showed that MK2i-NP cellular uptake involves both macropinocytosis and clathrin mediated endocytosis, whereas the free peptide exclusively utilizes clathrin mediated endocytosis for cell entry. Scanning electron microscopy studies revealed that MK2i-NPs, but not free MK2i peptide, induce cellular membrane ruffling consistent with macropinocytosis. TEM confirmed that MK2i-NPs induce macropinosome formation and achieve MK2i endo-lysosomal escape and cytosolic delivery. Finally, a novel technique based on recruitment of Galectin-8-YFP was utilized to demonstrate that MK2i-NPs cause endosomal disruption within 30 minutes of uptake. These new insights on the relationship between NP physicochemical properties and cellular uptake and trafficking can potentially be applied to further optimize the MK2i-NP system and more broadly toward the rational engineering of nano-scale constructs for the intracellular delivery of biologic drugs.
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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.