Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery.
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.
Lomas
Hannah
H
Biomaterials and Tissue Engineering Group, Department of Engineering Materials, University of Sheffield, The Kroto Research Institute, Broad Lane, Sheffield, UK S3 7HQ.
Massignani
Marzia
M
Abdullah
Khairuddin A
KA
Canton
Irene
I
Lo Presti
Caterina
C
MacNeil
Sheila
S
Du
Jianzhong
J
Blanazs
Adam
A
Madsen
Jeppe
J
Armes
Steven P
SP
Lewis
Andrew L
AL
Battaglia
Giuseppe
G
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
D008689:Methacrylates; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); D010767:Phosphorylcholine; D004247:DNA