Surface functionalisation of PLGA nanoparticles for gene silencing

被引：43

作者：

Andersen, Morten O. ^{[1
,2
]}

Lichawska, Agata ^{[1
,2
]}

Arpanaei, Ayyoob ^{[1
]}

Jensen, Stig Moller Rask ^{[1
,2
]}

Kaur, Harpreet ^{[3
]}

Oupicky, David ^{[3
]}

Besenbacher, Flemming ^{[1
]}

Kingshott, Peter ^{[1
]}

Kjems, Jorgen ^{[1
,2
]}

Howard, Kenneth A. ^{[1
,2
]}

机构：

[1] Univ Aarhus, Interdisciplinary Nanosci Ctr INANO, DK-8000 Aarhus, Denmark

[2] Univ Aarhus, Dept Mol Biol, DK-8000 Aarhus, Denmark

[3] Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI 48202 USA

来源：

BIOMATERIALS | 2010年 / 31卷 / 21期

关键词：

RNAi; siRNA; PLGA; Cetylated PEI; Drug delivery; Surface modification; POLY(D; L-LACTIC-CO-GLYCOLIC ACID) MICROSPHERES; BCL-2 FAMILY PROTEINS; PLASMID DNA; IN-VIVO; DELIVERY; POLYETHYLENIMINE; SIRNA; MICROPARTICLES; SYSTEM; TRANSFECTION;

D O I：

10.1016/j.biomaterials.2010.03.069

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI formulations (6.5 and 2.5% surface nitrogen, respectively). The modified particles were shown by spectroscopy, fluorescent microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular, toxicity. In addition, particles containing cetylated-PEI achieved 64% silencing of TNF alpha in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5671 / 5677

页数：7

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