Improved SiRNA Delivery Efficiency Via Solvent-induced Condensation of Micellar Nanoparticles

Overview

Journal Nanotechnology

Specialty Biotechnology

Date 2017 Mar 8

PMID 28266928

Citations 2

Authors

Juan Wu

Wei Qu

John-Michael Williford

Yong Ren

Xuesong Jiang

Xuan Jiang

Deng Pan

Hai-Quan Mao

Erik Luijten

Affiliations

Soon will be listed here.

Abstract

Efficient delivery of short interfering RNA (siRNA) remains one of the primary challenges of RNA interference therapy. Polyethylene glycol (PEG)ylated polycationic carriers have been widely used for the condensation of DNA and RNA molecules into complex-core micelles. The PEG corona of such nanoparticles can significantly improve their colloidal stability in serum, but PEGylation of the carriers also reduces their condensation capacity, hindering the generation of micellar particles with sufficient complex stability. This presents a particularly significant challenge for packaging siRNA into complex micelles, as it has a much smaller size and more rigid chain structure than DNA plasmids. Here, we report a new method to enhance the condensation of siRNA with PEGylated linear polyethylenimine using organic solvent and to prepare smaller siRNA nanoparticles with a more extended PEG corona and consequently higher stability. As a proof of principle, we have demonstrated the improved gene knockdown efficiency resulting from the reduced siRNA micelle size in mice livers following intravenous administration.

Citing Articles

Polydopamine-based nanoparticles with excellent biocompatibility for photothermally enhanced gene delivery.

Zhang P, Xu Q, Du J, Wang Y RSC Adv. 2022; 8(60):34596-34602.

PMID: 35548626 PMC: 9086945. DOI: 10.1039/c8ra06916f.

A facile strategy for fine-tuning the stability and drug release of stimuli-responsive cross-linked micellar nanoparticles towards precision drug delivery.

Xiao K, Lin T, Lam K, Li Y Nanoscale. 2017; 9(23):7765-7770.

PMID: 28585953 PMC: 5568647. DOI: 10.1039/c7nr02530k.

References

Maruyama H, Higuchi N, Nishikawa Y, Kameda S, Iino N, Kazama J . High-level expression of naked DNA delivered to rat liver via tail vein injection. J Gene Med. 2002; 4(3):333-41. DOI: 10.1002/jgm.281. View

Akinc A, Thomas M, Klibanov A, Langer R . Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J Gene Med. 2004; 7(5):657-63. DOI: 10.1002/jgm.696. View

Chen D, Jiang M . Strategies for constructing polymeric micelles and hollow spheres in solution via specific intermolecular interactions. Acc Chem Res. 2005; 38(6):494-502. DOI: 10.1021/ar040113d. View

Owens 3rd D, Peppas N . Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2005; 307(1):93-102. DOI: 10.1016/j.ijpharm.2005.10.010. View

Mao S, Neu M, Germershaus O, Merkel O, Sitterberg J, Bakowsky U . Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes. Bioconjug Chem. 2006; 17(5):1209-18. DOI: 10.1021/bc060129j. View

Yuan Y, Pei Y, Chen H, Tuschl T, Patel D . A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA. Structure. 2006; 14(10):1557-65. PMC: 4692372. DOI: 10.1016/j.str.2006.08.009. View

Bumcrot D, Manoharan M, Koteliansky V, Sah D . RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol. 2006; 2(12):711-9. PMC: 7097247. DOI: 10.1038/nchembio839. View

Hsiao P, Luijten E . Salt-induced collapse and reexpansion of highly charged flexible polyelectrolytes. Phys Rev Lett. 2006; 97(14):148301. DOI: 10.1103/PhysRevLett.97.148301. View

Arkhipov A, Freddolino P, Schulten K . Stability and dynamics of virus capsids described by coarse-grained modeling. Structure. 2006; 14(12):1767-77. DOI: 10.1016/j.str.2006.10.003. View

10.

Herweijer H, Wolff J . Gene therapy progress and prospects: hydrodynamic gene delivery. Gene Ther. 2006; 14(2):99-107. DOI: 10.1038/sj.gt.3302891. View

11.

Kim S, Shin D, Choi T, Lee J, Cheon G, Kim K . Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. Mol Ther. 2007; 15(6):1145-52. DOI: 10.1038/sj.mt.6300168. View

12.

Sanders L, Xian W, Guaqueta C, Strohman M, Vrasich C, Luijten E . Control of electrostatic interactions between F-actin and genetically modified lysozyme in aqueous media. Proc Natl Acad Sci U S A. 2007; 104(41):15994-9. PMC: 2042150. DOI: 10.1073/pnas.0705898104. View

13.

Guaqueta C, Luijten E . Polyelectrolyte condensation induced by linear cations. Phys Rev Lett. 2007; 99(13):138302. DOI: 10.1103/PhysRevLett.99.138302. View

14.

Arkhipov A, Yin Y, Schulten K . Four-scale description of membrane sculpting by BAR domains. Biophys J. 2008; 95(6):2806-21. PMC: 2527247. DOI: 10.1529/biophysj.108.132563. View

15.

Castanotto D, Rossi J . The promises and pitfalls of RNA-interference-based therapeutics. Nature. 2009; 457(7228):426-33. PMC: 2702667. DOI: 10.1038/nature07758. View

16.

Akinc A, Goldberg M, Qin J, Dorkin J, Gamba-Vitalo C, Maier M . Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol Ther. 2009; 17(5):872-9. PMC: 2835134. DOI: 10.1038/mt.2009.36. View

17.

Howard K . Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev. 2009; 61(9):710-20. DOI: 10.1016/j.addr.2009.04.001. View

18.

Osada K, Christie R, Kataoka K . Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. J R Soc Interface. 2009; 6 Suppl 3:S325-39. PMC: 2690088. DOI: 10.1098/rsif.2008.0547.focus. View

19.

Hallett F, Watton J, Krygsman P . Vesicle sizing: Number distributions by dynamic light scattering. Biophys J. 2009; 59(2):357-62. PMC: 1281152. DOI: 10.1016/S0006-3495(91)82229-9. View

20.

Merkel O, Beyerle A, Librizzi D, Pfestroff A, Behr T, Sproat B . Nonviral siRNA delivery to the lung: investigation of PEG-PEI polyplexes and their in vivo performance. Mol Pharm. 2009; 6(4):1246-60. DOI: 10.1021/mp900107v. View