title: Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells.
abstract: There is an emerging need both in pharmacology and within the biomedical industry to develop new tools to target intracellular mechanisms. The efficient delivery of functionally active proteins within cells is potentially a powerful research strategy, especially through the use of antibodies. In this work, we report on a nanovector for the efficient encapsulation and delivery of antibodies into live cells with no significant loss of cell viability or any deleterious effect on cell metabolic activity. This delivery system is based on poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-[2-(diisopropylamino)ethyl methacrylate] (PMPC-PDPA), a pH-sensitive diblock copolymer that self-assembles to form nanometer-sized vesicles, also known as polymersomes, at physiological pH. Polymersomes can successfully deliver relatively high antibody payloads within different types of live cells. We demonstrate that these antibodies can target their respective epitope showing immunolabeling of γ-tubulin, actin, Golgi protein, and the transcription factor NF-κB in live cells. Finally, we demonstrate that intracellular delivery of antibodies can control specific subcellular events, as well as modulate cell activity and proinflammatory processes.
authors.affiliation: The Krebs Institute, University of Sheffield, Sheffield, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Canton
authors.forename: Marzia
authors.initials: M
authors.lastname: Massignani
authors.forename: Nisa
authors.initials: N
authors.lastname: Patikarnmonthon
authors.forename: Luca
authors.initials: L
authors.lastname: Chierico
authors.forename: James
authors.initials: J
authors.lastname: Robertson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Renshaw
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Warren
authors.forename: Jeppe P
authors.initials: JP
authors.lastname: Madsen
authors.forename: Steven P
authors.initials: SP
authors.lastname: Armes
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013347:Subcellular Fractions / Q000276:immunology
chemical_list: D000906:Antibodies; D011109:Polymethacrylic Acids; C578682:poly(2-(methacryloyloxy)ethyl phosphorylcholine)-block-(2-(diisopropylamino)ethyl methacrylate); D010767:Phosphorylcholine