Poly-L-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery

被引:241
|
作者
Hartono, Sandy B. [2 ]
Gu, Wenyi [2 ]
Kleitz, Freddy [4 ,5 ]
Liu, Jian [2 ]
He, Lizhong [1 ]
Middelberg, Anton P. J. [1 ]
Yu, Chengzhong [2 ]
Lu, Gao Qing [2 ]
Qiao, Shi Zhang [2 ,3 ]
机构
[1] Univ Queensland, Ctr Biomol Engn, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
[2] Univ Queensland, ARC Ctr Excellence Funct Nanomat, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
[3] Univ Adelaide, Sch Chem Engn, Adelaide, SA 5005, Australia
[4] Univ Laval, Dept Chem, Quebec City, PQ G1V 0A6, Canada
[5] Univ Laval, Ctr Rech Mat Avances CERMA, Quebec City, PQ G1V 0A6, Canada
基金
澳大利亚研究理事会; 加拿大自然科学与工程研究理事会;
关键词
mesoporous silica nanoparticles; poly-L-lysine; gene delivery; siRNA; cellular uptake; MESOPOROUS SILICA; DRUG-DELIVERY; DNA COMPLEXES; SIRNA; ADSORPTION; VECTOR; NANOMEDICINE; DOXORUBICIN; POLYLYSINE; FUSION;
D O I
10.1021/nn2039643
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-L-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100-200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state C-13 magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 mu g/mL.
引用
收藏
页码:2104 / 2117
页数:14
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