Poly(L-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides.
Silica nanoparticles were prepared in a microemulsion system, using polyoxyethylene nonylphenyl ether/cyclohexane/ammonium hydroxide. The surface charge of the particle was modified with PLL [poly(L-lysine)]. PAGE demonstrated the ability of PMS-NP (PLL-modified silica nanoparticles) to bind and protect antisense ODNs (oligonucleotides). The intracellular localization of FITC-labelled ODN was investigated by fluorescence microscopy. The results demonstrated that ODN could be delivered to cytoplasm. Flow-cytometry analysis showed a 20-fold enhancement of ODN delivered by PMS-NP compared with free ODN for a serum-free medium. Blocking efficacy of c- myc antisense ODN, delivered by PMS-NP, was examined in HNE1 and HeLa cell lines. Significant down-regulation of c- myc mRNA levels was observed in both the cell lines. However, the cellular uptake efficiency and antisense effects on target gene decreased in the presence of serum-containing medium. The analysis of the filtration assay showed that PMS-NP interacted with serum proteins. These results indicated that PMS-NP was a suitable delivery vector for antisense ODN, although its delivery efficiency decreased in the presence of a serum-containing medium.
Zhu
Shi-Guo
SG
Cancer Research Institute, XiangYa School of Medicine, Central South University, ChangSha, HuNan 410078, People's Republic of China.
Xiang
Juan-Juan
JJ
Li
Xiao-Ling
XL
Shen
Shou-Rong
SR
Lu
Hong-Bin
HB
Zhou
Jie
J
Xiong
Wei
W
Zhang
Bi-Cheng
BC
Nie
Xin-Min
XM
Zhou
Ming
M
Tang
Ke
K
Li
Gui-Yuan
GY
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D020320:Oligoribonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics; D010316:Particle Size; D011107:Polylysine / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D020320:Oligoribonucleotides, Antisense; D011107:Polylysine; D012822:Silicon Dioxide