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磷酸钙纳米颗粒作为一种新型非病毒载体用于癌症基因治疗中DNA的高效转染。

Calcium phosphate nanoparticles as a novel nonviral vector for efficient transfection of DNA in cancer gene therapy.

作者信息

Liu Ting, Tang Aifa, Zhang Guiying, Chen Yuxiang, Zhang Junyi, Peng Shusong, Cai Zhiming

机构信息

Xiangya Hospital, Central South University, Changsha 410078, Hunan Province, People's Republic of China.

出版信息

Cancer Biother Radiopharm. 2005 Apr;20(2):141-9. doi: 10.1089/cbr.2005.20.141.

Abstract

To explore an efficient gene vector in cancer gene therapy, a novel nonviral vector calcium phosphate nanoparticle (CPNP) was developed. Transmission electromicroscopy and Zeta potential demonstrated that CPNP was 23.5-34.5 nm diameters and had +16.8 mV positive surface charges. The analysis of the CPNPDNA complex showed CPNP could transfer foreign DNA into targeted cells with high transfection efficiency, as well as its DNA-binding property and protection of DNA from degradation. Furthermore, the CPNP-DNA complex had no obvious cytotoxicity for CNE-2 cells, while the liposome-DNA complex had certain cytotoxicity. When the CPNP combined with suicide genes yCDglyTK for nasopharyngeal carcinoma (NPC) therapy in vitro, just 24.76% of cells survived when the wild-type CNE-2 cells were treated with the CPNP-yCDglyTK complex plus the prodrug, 5-FC (200 mg/mL). Otherwise, the expression of yCDglyTK was detected in implanted CNE-2 tumors by reverse transcription-polymerase chain reaction (RT-PCR) analysis when the CNE-2 tumor was treated with an intratumoral injection of the CPNPyCDglyTK complex. Our results showed that the CPNP might be a potential vector for gene therapy.

摘要

为了在癌症基因治疗中探索一种高效的基因载体,开发了一种新型非病毒载体磷酸钙纳米颗粒(CPNP)。透射电子显微镜和Zeta电位显示CPNP直径为23.5 - 34.5 nm,表面带 +16.8 mV的正电荷。对CPNP-DNA复合物的分析表明,CPNP能够以高转染效率将外源DNA转移到靶细胞中,同时具有DNA结合特性并能保护DNA不被降解。此外,CPNP-DNA复合物对CNE-2细胞没有明显的细胞毒性,而脂质体-DNA复合物具有一定的细胞毒性。当CPNP与自杀基因yCDglyTK联合用于体外鼻咽癌(NPC)治疗时,用CPNP-yCDglyTK复合物加前药5-FC(200 mg/mL)处理野生型CNE-2细胞时,仅有24.76%的细胞存活。另外,当用瘤内注射CPNP-yCDglyTK复合物处理CNE-2肿瘤时,通过逆转录-聚合酶链反应(RT-PCR)分析在植入的CNE-2肿瘤中检测到了yCDglyTK的表达。我们的结果表明CPNP可能是一种潜在的基因治疗载体。

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