Theranostic poly(lactic-co-glycolic acid) nanoparticle for magnetic resonance/infrared fluorescence bimodal imaging and efficient siRNA delivery to macrophages and its evaluation in a kidney injury model

被引:27
作者
Yang, Chuanxu [1 ,2 ]
Hieu Vu-Quang [1 ,2 ]
Husum, Dina Michelle Unnerup [3 ]
Tingskov, Stine Julie [3 ]
Vinding, Mads Sloth [1 ]
Nielsen, Thomas [4 ]
Song, Ping [1 ]
Nielsen, Niels Chr. [1 ]
Norregaard, Rikke [3 ]
Kjems, Jorgen [1 ,2 ]
机构
[1] Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, Aarhus C, Denmark
[2] Aarhus Univ, Dept Mol Biol & Genet, Aarhus C, Denmark
[3] Aarhus Univ Hosp, Dept Clin Med, Aarhus N, Denmark
[4] Aarhus Univ Hosp, Ctr Functionally Integrat Neurosci, Aarhus C, Denmark
关键词
Theranostics; PLGA; Indocyanine green; Iron oxides; siRNA delivery; MESOPOROUS SILICA NANOPARTICLES; MESENCHYMAL STEM-CELLS; IN-VIVO; PLGA NANOPARTICLES; GENE DELIVERY; NANOMEDICINE STRATEGIES; INFLAMMATORY DISEASES; TARGETED DELIVERY; INDOCYANINE GREEN; RENAL-DISEASE;
D O I
10.1016/j.nano.2017.08.007
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
In this work, a theranostic nanoparticle was developed for multimodal imaging and siRNA delivery. The core of the nanoparticles (NP) was formed by encapsulation of superparamagnetic iron oxides and indocyanine green in a PLGA matrix to serve as a multimodal probe for near-infrared (NIFR) and magnetic resonance (MR) imaging. The surface of the particle was coated with polyethylenimine (PEI) for siRNA delivery. Macrophages efficiently took up the nanoparticles and emitted strong NIFR and MR contrast. When transfected with siRNA targeting the pro-inflammatory enzyme cyclooxygenase-2 (COX-2), significant down-regulation of COX-2 was achieved in activated macrophages. Furthermore, after injection into a unilateral ureteral obstruction (UUO)-induced kidney injury model, NIFR and MRI imaging revealed accumulation of nanoparticles in the injury kidney. In addition, in vivo silencing of COX-2 was achieved by NP/PEI/siCOX-2, which further attenuated kidney injury. Our theranostic platform represents a promising approach for simultaneous diagnosis and treatment of inflammatory diseases. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:2451 / 2462
页数:12
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