Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction Mediated Drug Delivery to Specific Cell Populations
| Autor: | Amanda I. Meriwether, Chi Zhao, Hugh D. C. Smyth, Janet Zoldan, Jeanne C. Stachowiak, Avinash K. Gadok, Tanner G. Rowley, Silvia Ferrati |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Surface Properties Drug Compounding Recombinant Fusion Proteins Population Cell Biology Ligands Biochemistry Membrane Fusion Models Biological Article 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Cell-Derived Microparticles medicine Humans education Receptor education.field_of_study Antibiotics Antineoplastic Gap junction Gap Junctions Single-Domain Antibodies Small molecule Molecular biology Transmembrane protein Cell biology Luminescent Proteins Protein Transport 030104 developmental biology medicine.anatomical_structure HEK293 Cells Microscopy Fluorescence Cytoplasm Doxorubicin 030220 oncology & carcinogenesis Drug delivery Antibodies Immobilized HeLa Cells |
| Popis: | Gap junctions, transmembrane protein channels that directly connect the cytoplasm of neighboring cells and enable the exchange of molecules between cells, are a promising new frontier for therapeutic delivery. Specifically, cell-derived lipid vesicles that contain functional gap junction channels, termed Connectosomes, have recently been demonstrated to substantially increase the effectiveness of small molecule chemotherapeutics. However, because gap junctions are present in nearly all tissues, Connectosomes have no intrinsic ability to target specific cell types, which potentially limits their therapeutic effectiveness. To address this challenge, here we display targeting ligands consisting of single-domain antibodies on the surfaces of Connectosomes. We demonstrate that these targeted Connectosomes selectively interact with cells that express a model receptor, promoting the selective delivery of the chemotherapeutic doxorubicin to this target cell population. More generally, our approach has the potential to boost cytoplasmic delivery of diverse therapeutic molecules to specific cell populations while protecting off-target cells, a critical step toward realizing the therapeutic potential of gap junctions. |
| Databáze: | OpenAIRE |
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