Targeted cationic poly(D,L-lactic-co-glycolic acid) nanoparticles for gene delivery to cultured cells.
Targeted cationic poly(D,L-lactic-co-glycolic acid) nanoparticles for gene delivery to cultured cells.
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DOI：
10.2478/s11658-009-0003-7
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发表时间：
2009
影响因子：
8.3
通讯作者：
Tros de Ilarduya C
中科院分区：
文献类型：
--
作者：
Díez S;Miguéliz I;Tros de Ilarduya C
我们开发了一种由聚(D，L-乳酸-乙醇酸)(PLGA)、1，2-二油酰基-3-(三甲基铵)丙烷(DOTAP)和去唾液酸(AF)组成的新型靶向阳离子纳米粒子体系，发现它是一种高效的肝癌基因递送制剂。通过改进的溶剂挥发法制备了纳米粒子(NP)，该方法采用两种方案来包裹(NP1粒子)或吸附(NP2粒子)质粒DNA。最终的粒子在纳米级的范围内。负载效率较高的PLGA/DOTAP/AF粒子表面带正电荷。与游离DNA和普通(非靶向)系统相比，携带荧光素酶和白介素12(IL-12)编码基因的靶向积雪草素纳米粒(AF-NP)即使在60%的胎牛血清(FBS)存在的情况下，也能提高转染率。在去唾液酸糖蛋白受体(ASGPr-)缺陷的HeLa细胞上进行的转基因结果证实了受体介导的内吞机制。综上所述，这是第一次通过携带治疗性基因IL-12的PLGA/DOTAP/DNA纳米粒靶向去唾液酸糖蛋白受体，在很高浓度的血清存在下有效地将基因输送到肝癌细胞，这可能是一种潜在的体内应用系统。
We developed a new targeted cationic nanoparticulate system composed of poly(D,L-lactic-co-glycolic acid) (PLGA), 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP) and asialofetuin (AF), and found it to be a highly effective formulation for gene delivery to liver tumor cells. The nanoparticles (NP) were prepared by a modified solvent evaporation process that used two protocols in order to encapsulate (NP1 particles) or adsorb (NP2 particles) plasmid DNA. The final particles are in the nanoscale range. pDNA loaded in PLGA/DOTAP/AF particles with high loading efficiency showed a positive surface charge. Targeted asialofetuin-nanoparticles (AF-NP) carrying genes encoding for luciferase and interleukin-12 (IL-12) resulted in increased transfection efficiencies compared to free DNA and to plain (non-targeted) systems, even in the presence of 60% fetal bovine serum (FBS). The results of transfections performed on HeLa cells, defective in asialoglycoprotein receptors (ASGPr-), confirmed the receptor-mediated endocytosis mechanism. In summary, this is the first time that asialoglycoprotein receptor targeting by PLGA/DOTAP/DNA nanoparticles carrying the therapeutic gene IL-12 has been shown to be efficient in gene delivery to liver cancer cells in the presence of a very high concentration of serum, and this could be a potential system for in vivo application.
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影响因子：
10.8
作者：
Leong, KW;Mao, HQ;August, JT
通讯作者：
August, JT
影响因子：
5.1
作者：
Arangoa, MA;Düzgünes, N;de Ilarduya, CT
通讯作者：
de Ilarduya, CT
影响因子：
5.1
作者：
Eliyahu, H;Servel, N;Barenholz, Y
通讯作者：
Barenholz, Y
影响因子：
13.5
作者：
MARTINEZFONG, D;MULLERSMAN, JE;MARTINEZHERNANDEZ, A
通讯作者：
MARTINEZHERNANDEZ, A
影响因子：
10.8
作者：
Jeong, JH;Park, TG
通讯作者：
Park, TG