PMID- 27294846 OWN - NLM STAT- MEDLINE DCOM- 20180129 LR - 20181202 IS - 1613-6829 (Electronic) IS - 1613-6810 (Print) IS - 1613-6810 (Linking) VI - 12 IP - 28 DP - 2016 Jul TI - Multifunctional Transmembrane Protein Ligands for Cell-Specific Targeting of Plasma Membrane-Derived Vesicles. PG - 3837-48 LID - 10.1002/smll.201600493 [doi] AB - Liposomes and nanoparticles that bind selectively to cell-surface receptors can target specific populations of cells. However, chemical conjugation of ligands to these particles is difficult to control, frequently limiting ligand uniformity and complexity. In contrast, the surfaces of living cells are decorated with highly uniform populations of sophisticated transmembrane proteins. Toward harnessing cellular capabilities, here it is demonstrated that plasma membrane vesicles (PMVs) derived from donor cells can display engineered transmembrane protein ligands that precisely target cells on the basis of receptor expression. These multifunctional targeting proteins incorporate (i) a protein ligand, (ii) an intrinsically disordered protein spacer to make the ligand sterically accessible, and (iii) a fluorescent protein domain that enables quantification of the ligand density on the PMV surface. PMVs that display targeting proteins with affinity for the epidermal growth factor receptor (EGFR) bind at increasing concentrations to breast cancer cells that express increasing levels of EGFR. Further, as an example of the generality of this approach, PMVs expressing a single-domain antibody against green fluorescence protein (eGFP) bind to cells expressing eGFP-tagged receptors with a selectivity of approximately 50:1. The results demonstrate the versatility of PMVs as cell targeting systems, suggesting diverse applications from drug delivery to tissue engineering. CI - (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Zhao, Chi AU - Zhao C AD - Department of Biomedical Engineering, Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712, USA. FAU - Busch, David J AU - Busch DJ AD - Department of Biomedical Engineering, Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712, USA. FAU - Vershel, Connor P AU - Vershel CP AD - Department of Biomedical Engineering, Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712, USA. FAU - Stachowiak, Jeanne C AU - Stachowiak JC AD - Department of Biomedical Engineering, Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX, 78712, USA. LA - eng GR - R01 GM112065/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20160613 PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 RN - 0 (Liposomes) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - CHO Cells MH - Cell Line, Tumor MH - Cell Membrane/*chemistry/*metabolism MH - Cricetulus MH - Drug Delivery Systems MH - ErbB Receptors/chemistry MH - Humans MH - Liposomes/chemistry MH - Tissue Engineering PMC - PMC5523125 MID - NIHMS880840 OTO - NOTNLM OT - biomaterials OT - cell targeting OT - extracellular vesicles OT - protein engineering EDAT- 2016/06/14 06:00 MHDA- 2018/01/30 06:00 PMCR- 2017/07/24 CRDT- 2016/06/14 06:00 PHST- 2016/02/15 00:00 [received] PHST- 2016/04/18 00:00 [revised] PHST- 2016/06/14 06:00 [entrez] PHST- 2016/06/14 06:00 [pubmed] PHST- 2018/01/30 06:00 [medline] PHST- 2017/07/24 00:00 [pmc-release] AID - 10.1002/smll.201600493 [doi] PST - ppublish SO - Small. 2016 Jul;12(28):3837-48. doi: 10.1002/smll.201600493. Epub 2016 Jun 13.