Large-pore mesoporous silica nanospheres as vehicles for delivering TRAF3-shRNA plasmids to Kupffer cells

Journal Article · Fri Jan 08 00:00:00 EST 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.11.101· OSTI ID:22594164

Zhang, Junyong ^[1]; Guo, Shipeng ^[2]; Zhang, Wenfeng ^[2]; Niu, Dechao ^[3]; Gong, Jianping ^[2]

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1. Department of Hepatobiliary Surgery and Department of Urinary Surgery, The Second Affiliated Hospital of Chongqing Medical University (China)
2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University (China)
3. Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology (China)

The currently available techniques for transferring exogenous genes into macrophages, especially the targeted import of exogenous genes into Kupffer cells (KCs) in vivo, are inefficient and achieve only low targeting. Novel Large-Pore Mesoporous Silica Nanospheres (LPMSNs) may be a promising gene transfection agent for KCs because of their superior biodegradation and hypotoxic characteristics, as well as their ability to retain the biological function of KCs and the high loading-rate of exogenous plasmid. LPMSNs were able to completely adsorb shRNA-TRAF3 (tumor necrosis factor receptor-associated factor-3) plasmid at a mass ratio as low as 30:1, and exhibited a low cytotoxicity for KCs. LPMSNs were detected in KC cytoplasm in vitro, and transmission electron microscopy (TEM) revealed that they were present only in KCs in liver tissue in vivo. The max KC transfection efficiency with LPMSNs was 34.8± 0.07%, as evaluated using flow cytometry, and the protein and mRNA levels of TRAF3 were significantly inhibited (P < 0.05) by shRNA-TRAF3 plasmid transfection after 24 h in vitro and 48 h in vivo. In conclusion, KC targeted transfection was achieved successfully by LPMSNs carrying shRNA-TRAF3 plasmids in vitro and vivo. The protein and mRNA levels of TRAF3 were suppressed significantly. These results suggest that LPMSNs are a promising vehicle for delivering exogenous genes into KCs in vitro and vivo. - Highlights: • We constructed Large-Pore Mesoporous Silica Nanospheres (LPMSNs). • LPMSNs adsorbed high quantity of plasmid. • Low cytotoxicity of LPMSNs to Kupffer cells. • LPMSNs delivered plasmid into Kupffer cells.

• OSTI ID: 22594164
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 469, Issue 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIODEGRADATION
BIOLOGICAL FUNCTIONS
CYTOPLASM
DNA
FLUORESCENCE
GENES
IN VITRO
IN VIVO
LIPOPOLYSACCHARIDES
LIVER
MACROPHAGES
MESSENGER-RNA
NANOMATERIALS
NANOSTRUCTURES
NECROSIS
NEOPLASMS
PLASMIDS
POLYMERASE CHAIN REACTION
RADIOPROTECTIVE SUBSTANCES
RECEPTORS
RETICULOENDOTHELIAL SYSTEM
SILICA
TOXICITY
TRANSMISSION ELECTRON MICROSCOPY