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

Nanomedicine. 2017 Nov;13(8):2451-2462. doi: 10.1016/j.nano.2017.08.007. Epub 2017 Aug 24.

Abstract

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.

Keywords: Indocyanine green; Iron oxides; PLGA; Theranostics; siRNA delivery.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / genetics
  • Drug Carriers / chemistry*
  • Lactic Acid / chemistry*
  • Macrophages / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Optical Imaging / methods
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RAW 264.7 Cells
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use
  • RNAi Therapeutics / methods
  • Renal Insufficiency / genetics
  • Renal Insufficiency / therapy*
  • Theranostic Nanomedicine / methods
  • Transfection / methods

Substances

  • Drug Carriers
  • RNA, Small Interfering
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Cyclooxygenase 2