title: Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery.
abstract: We have recently achieved efficient cytosolic delivery by using pH-sensitive poly(2-(methacryloyloxy)ethylphosphorylcholine)-co-poly(2-(diisopropylamino)ethylmethacrylate) (PMPC-PDPA) diblock copolymers that self-assemble to form vesicles, known as polymersomes, in aqueous solution. It is particularly noteworthy that these diblock copolymers form stable polymersomes at physiological pH but rapidly dissociate below pH 6 to give molecularly-dissolved copolymer chains (unimers). These PMPC-PDPA polymersomes are used to encapsulate nucleic acids for efficient intracellular delivery. Confocal laser scanning microscopy and fluorescence flow cytometry are used to quantify cellular uptake and to study the kinetics of this process. Finally, we examine how PMPC-PDPA polymersomes affect the viability of primary human cells (human dermal fibroblasts (HDF)), paying particular regard to whether inflammatory responses are triggered.
authors.affiliation: Biomaterials and Tissue Engineering Group, Department of Engineering Materials, University of Sheffield, The Kroto Research Institute, Broad Lane, Sheffield, UK S3 7HQ.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lomas
authors.forename: Marzia
authors.initials: M
authors.lastname: Massignani
authors.forename: Khairuddin A
authors.initials: KA
authors.lastname: Abdullah
authors.forename: Irene
authors.initials: I
authors.lastname: Canton
authors.forename: Caterina
authors.initials: C
authors.lastname: Lo Presti
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Du
authors.forename: Adam
authors.initials: A
authors.lastname: Blanazs
authors.forename: Jeppe
authors.initials: J
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: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008689:Methacrylates; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); D010767:Phosphorylcholine; D004247:DNA