Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment

Ying Jiang; Joseph Hardie; Yuanchang Liu; Moumita Ray; Xiang Luo; Riddha Das; Ryan F Landis; Michelle E Farkas; Vincent M Rotello

doi:10.1016/j.jconrel.2018.06.001

Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment

J Control Release. 2018 Aug 10:283:235-240. doi: 10.1016/j.jconrel.2018.06.001. Epub 2018 Jun 5.

Authors

Ying Jiang¹, Joseph Hardie², Yuanchang Liu³, Moumita Ray⁴, Xiang Luo⁵, Riddha Das⁶, Ryan F Landis⁷, Michelle E Farkas⁸, Vincent M Rotello⁹

Affiliations

¹ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: yingj@chem.umass.edu.
² Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: jhardie@chem.umass.edu.
³ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: yuanchangliu@chem.umass.edu.
⁴ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: moumita@chem.umass.edu.
⁵ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA; ShenYang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, China. Electronic address: xiangluo@umass.edu.
⁶ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: riddhadas@chem.umass.edu.
⁷ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: rlandis@chem.umass.edu.
⁸ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: farkas@chem.umass.edu.
⁹ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: rotello@chem.umass.edu.

Abstract

The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.28 mg/kg. Significantly, the delivery of siRNA targeting tumor necrosis factor-α efficiently silenced TNF-α expression in LPS-challenged mice, demonstrating efficacy in modulating immune response in an organ-selective manner. This research highlights the potential of the NPSC platform for targeted immunotherapy and further manipulation of the immune system.

Keywords: Cytokine; Cytosolic delivery; Immunomodulation; Inflammation; siRNA delivery.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-Inflammatory Agents / administration & dosage*
Cytosol
Female
Gene Silencing
Mice
Mice, Inbred BALB C
Nanocapsules / administration & dosage*
RAW 264.7 Cells
RNA, Small Interfering / administration & dosage*
Tumor Necrosis Factor-alpha / genetics*

Substances

Anti-Inflammatory Agents
Nanocapsules
RNA, Small Interfering
Tumor Necrosis Factor-alpha

Abstract

Publication types

MeSH terms

Substances

Grants and funding