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Acta Biomater. 2018 Aug;76:164-177. doi: 10.1016/j.actbio.2018.05.054. Epub 2018 Jun 15.

Sustained delivery of siRNA/mesoporous silica nanoparticle complexes from nanofiber scaffolds for long-term gene silencing.

Author information

1
School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459 Singapore, Singapore; Artificial Biopolymers Department, Max Mousseron Institute of Biomolecules (IBMM), UMR CNRS 5247, University of Montpellier, Faculty of Pharmacy, Montpellier 34093, France.
2
School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459 Singapore, Singapore.
3
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
4
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
5
School of Chemical and Biomedical Engineering, Nanyang Technological University, 637459 Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232 Singapore, Singapore. Electronic address: sychew@ntu.edu.sg.

Abstract

A low toxicity and efficient delivery system is needed to deliver small interfering RNAs (siRNA) in vitro and in vivo. The use of mesoporous silica nanoparticles (MSN) is becoming increasingly common due to its biocompatibility, tunable pore size and customizable properties. However, bolus delivery of siRNA/MSN complexes remains suboptimal, especially when a sustained and long-term administration is required. Here, we utilized electrospun scaffolds for sustained delivery of siRNA/MSN-PEI through surface adsorption and nanofiber encapsulation. As a proof-of-concept, we targeted collagen type I expression to modulate fibrous capsule formation. Surface adsorption of siRNA/MSN-PEI provided sustained availability of siRNA for at least 30 days in vitro. As compared to conventional bolus delivery, such scaffold-mediated transfection provided more effective gene silencing (p < 0.05). On the contrary, a longer sustained release was attained (at least 5 months) when siRNA/MSN-PEI complexes were encapsulated within the electrospun fibers. In vivo subcutaneous implantation and biodistribution analysis of these scaffolds revealed that siRNA remained localized up to ∼290 μm from the implants. Finally, a fibrous capsule reduction of ∼45.8% was observed after 4 weeks in vivo as compared to negative scrambled siRNA treatment. Taken together, these results demonstrate the efficacy of scaffold-mediated sustained delivery of siRNA/MSN-PEI for long-term non-viral gene silencing applications.

STATEMENT OF SIGNIFICANCE:

The bolus delivery of siRNA/mesoporous silica nanoparticles (MSN) complexes shows high efficiency to silence protein agonists of tumoral processes as cancer treatments. However, in tissue engineering area, scaffold mediated delivery is desired to achieve a local and sustained release of therapeutics. We showed the feasibility and the efficacy of siRNA/MSN delivered from electrospun scaffolds through surface adsorption and nanofiber encapsulation. We showed that this method enhances siRNA transfection efficiency and sustained targeted proteins silencing in vitro and in vivo. As a proof of concept, in this study, we targeted collagen type I expression to modulate fibrous capsule formation. However this platform can be applied to the release and transfection of siRNA or miRNA in cancer and tissue engineering applications.

KEYWORDS:

Electrospinning; Foreign body reaction; Gene silencing; Host-implant integration

PMID:
29890267
DOI:
10.1016/j.actbio.2018.05.054
[Indexed for MEDLINE]

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