Nanocapsule-mediated Cytosolic SiRNA Delivery for Anti-inflammatory Treatment

Overview

Journal J Control Release

Specialty Pharmacology

Date 2018 Jun 9

PMID 29883695

Citations 16

Authors

Ying Jiang

Joseph Hardie

Yuanchang Liu

Moumita Ray

Xiang Luo

Riddha Das

Ryan F Landis

Michelle E Farkas

Vincent M Rotello

Affiliations

Soon will be listed here.

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.

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References

Jiang Y, Tang R, Duncan B, Jiang Z, Yan B, Mout R . Direct cytosolic delivery of siRNA using nanoparticle-stabilized nanocapsules. Angew Chem Int Ed Engl. 2014; 54(2):506-10. PMC: 4314441. DOI: 10.1002/anie.201409161. View

Ahsan F, Rivas I, Khan M, Torres Suarez A . Targeting to macrophages: role of physicochemical properties of particulate carriers--liposomes and microspheres--on the phagocytosis by macrophages. J Control Release. 2002; 79(1-3):29-40. DOI: 10.1016/s0168-3659(01)00549-1. View

Braet F, Wisse E, Bomans P, Frederik P, Geerts W, Koster A . Contribution of high-resolution correlative imaging techniques in the study of the liver sieve in three-dimensions. Microsc Res Tech. 2007; 70(3):230-42. DOI: 10.1002/jemt.20408. View

Blanco E, Shen H, Ferrari M . Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015; 33(9):941-51. PMC: 4978509. DOI: 10.1038/nbt.3330. View

Aouadi M, Tesz G, Nicoloro S, Wang M, Chouinard M, Soto E . Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature. 2009; 458(7242):1180-4. PMC: 2879154. DOI: 10.1038/nature07774. View

Medzhitov R . Origin and physiological roles of inflammation. Nature. 2008; 454(7203):428-35. DOI: 10.1038/nature07201. View

Whitehead K, Dorkin J, Vegas A, Chang P, Veiseh O, Matthews J . Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat Commun. 2014; 5:4277. PMC: 4111939. DOI: 10.1038/ncomms5277. View

Gordon S, Taylor P . Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5(12):953-64. DOI: 10.1038/nri1733. View

Chovatiya R, Medzhitov R . Stress, inflammation, and defense of homeostasis. Mol Cell. 2014; 54(2):281-8. PMC: 4048989. DOI: 10.1016/j.molcel.2014.03.030. View

10.

Joseph R, Srivastava O, Pfister R . Downregulation of β-actin and its regulatory gene HuR affect cell migration of human corneal fibroblasts. Mol Vis. 2014; 20:593-605. PMC: 4016806. View

11.

Mackenzie S, Espel E . Post-transcriptional regulation of TNF-alpha during in vitro differentiation of human monocytes/macrophages in primary culture. J Leukoc Biol. 2002; 71(6):1026-32. View

12.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood M . Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011; 29(4):341-5. DOI: 10.1038/nbt.1807. View

13.

Whitehead K, Langer R, Anderson D . Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009; 8(2):129-38. PMC: 7097568. DOI: 10.1038/nrd2742. View

14.

Yan B, Kim S, Kim C, Saha K, Moyano D, Xing Y . Multiplexed imaging of nanoparticles in tissues using laser desorption/ionization mass spectrometry. J Am Chem Soc. 2013; 135(34):12564-7. PMC: 3801209. DOI: 10.1021/ja406553f. View

15.

Lee H, Lytton-Jean A, Chen Y, Love K, Park A, Karagiannis E . Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol. 2012; 7(6):389-93. PMC: 3898745. DOI: 10.1038/nnano.2012.73. View

16.

Czapski G, Cakala M, Chalimoniuk M, Gajkowska B, Strosznajder J . Role of nitric oxide in the brain during lipopolysaccharide-evoked systemic inflammation. J Neurosci Res. 2007; 85(8):1694-703. DOI: 10.1002/jnr.21294. View

17.

Jiang Y, Huo S, Hardie J, Liang X, Rotello V . Progress and perspective of inorganic nanoparticle-based siRNA delivery systems. Expert Opin Drug Deliv. 2016; 13(4):547-59. PMC: 4914043. DOI: 10.1517/17425247.2016.1134486. View

18.

Tabas I, Glass C . Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science. 2013; 339(6116):166-72. PMC: 3608517. DOI: 10.1126/science.1230720. View

19.

Kim S, Ye C, Kumar P, Chiu I, Subramanya S, Wu H . Targeted delivery of siRNA to macrophages for anti-inflammatory treatment. Mol Ther. 2010; 18(5):993-1001. PMC: 2890121. DOI: 10.1038/mt.2010.27. View

20.

Gokhan Elci S, Tonga G, Yan B, Kim S, Kim C, Jiang Y . Dual-Mode Mass Spectrometric Imaging for Determination of in Vivo Stability of Nanoparticle Monolayers. ACS Nano. 2017; 11(7):7424-7430. PMC: 5767328. DOI: 10.1021/acsnano.7b03711. View