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Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing
นักวิจัย : Tan, Yang Fei , Mundargi, Raghavendra C. , Chen, Min Hui Averil , Lessig, Jacqueline , Neu, Björn , Venkatraman, Subbu S. , Wong, Tina T.
คำค้น : DRNTU::Engineering::Materials::Nanostructured materials
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2557
อ้างอิง : Tan, Y. F., Mundargi, R. C., Chen, M. H. A., Lessig, J., Neu, B., Venkatraman, S. S., & Wong, T. T. (2014). Layer-by-Layer Nanoparticles as an Efficient siRNA Delivery Vehicle for SPARC Silencing . Small, 10(9), 1790-1798. , 1613-6810 , http://hdl.handle.net/10220/19326 , http://dx.doi.org/10.1002/smll.201303201 , 178779
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Small
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO-siRNA and SPARC-siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC-gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT-PCR. The multilayer SPARC-siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC-gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real-time cell proliferation and MTT cell assay, indicated that the SPARC-siRNA-loaded LbL NPs are non-toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non-viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics.

บรรณานุกรม :
Tan, Yang Fei , Mundargi, Raghavendra C. , Chen, Min Hui Averil , Lessig, Jacqueline , Neu, Björn , Venkatraman, Subbu S. , Wong, Tina T. . (2557). Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Tan, Yang Fei , Mundargi, Raghavendra C. , Chen, Min Hui Averil , Lessig, Jacqueline , Neu, Björn , Venkatraman, Subbu S. , Wong, Tina T. . 2557. "Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Tan, Yang Fei , Mundargi, Raghavendra C. , Chen, Min Hui Averil , Lessig, Jacqueline , Neu, Björn , Venkatraman, Subbu S. , Wong, Tina T. . "Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2557. Print.
Tan, Yang Fei , Mundargi, Raghavendra C. , Chen, Min Hui Averil , Lessig, Jacqueline , Neu, Björn , Venkatraman, Subbu S. , Wong, Tina T. . Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2557.