4.6 Article

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

Journal

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 8, Pages 2451-2462

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.08.007

Keywords

Theranostics; PLGA; Indocyanine green; Iron oxides; siRNA delivery

Funding

  1. Lundbeck Foundation [23750]
  2. Danish Research Council for Independent Research-Medical Sciences [DFF-6110-00231]
  3. AUFF Starting Grant Associate Professor [AUFF-E-2015-FLS-8-69]

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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.

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