Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells

被引：61

作者：

Canton, Irene ^{[1
,2
,3
]}

Massignani, Marzia ^{[1
,3
]}

Patikarnmonthon, Nisa ^{[1
,2
,3
]}

Chierico, Luca ^{[1
,2
,3
]}

Robertson, James ^{[1
,2
,3
,4
]}

Renshaw, Stephen A. ^{[1
,4
,5
]}

Warren, Nicholas J. ^{[3
,6
]}

Madsen, Jeppe P. ^{[1
,2
,3
,6
]}

Armes, Steven P. ^{[6
]}

Lewis, Andrew L. ^{[7
]}

Battaglia, Giuseppe ^{[1
,2
,3
]}

机构：

[1] Univ Sheffield, Krebs Inst, Sheffield S10 2TN, S Yorkshire, England

[2] Univ Sheffield, Ctr Membrane Interact & Dynam, Sheffield S10 2TN, S Yorkshire, England

[3] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[4] Univ Sheffield, MRC, Ctr Dev & Biomed Genet, Sheffield S10 2TN, S Yorkshire, England

[5] Univ Sheffield, Dept Infect & Immun, Sheffield S10 2TN, S Yorkshire, England

[6] Univ Sheffield, Dept Chem, Sheffield S10 2TN, S Yorkshire, England

[7] Biocompatibles UK Ltd, Farnham, Surrey, England

来源：

FASEB JOURNAL | 2013年 / 27卷 / 01期

基金：

英国医学研究理事会;

关键词：

immunotargeting; protein; antibody; nanovector; NF-KAPPA-B; IN-VITRO; GENE DELIVERY; DNA; LOCALIZATION; COMPLEXES; SELECTION; CYTOKINE; THERAPY; MODEL;

D O I：

10.1096/fj.12-212183

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gamma-tubulin, actin, Golgi protein, and the transcription factor NF-kappa B 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.-Canton, I., Massignani, M., Patikarnmonthon, N., Chierico, L., Robertson, J., Renshaw, S. A., Warren, N. J., Madsen, J. P., Armes, S P., Lewis, A. L., Battaglia, G. Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells. FASEB J. 27, 98-108 (2013). www.fasebj.org

引用

页码：98 / 108

页数：11

共 41 条

[1] Heterogeneous requirement of IκB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis -: Implications for therapy [J].