Delivery of PUMA Apoptosis Gene Using Polyethyleneimine-SMCC-TAT/DNA Nanoparticles: Biophysical Characterization and In Vitro Transfection Into Malignant Melanoma Cells
Delivery of PUMA Apoptosis Gene Using Polyethyleneimine-SMCC-TAT/DNA Nanoparticles: Biophysical Characterization and In Vitro Transfection Into Malignant Melanoma Cells
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使用聚乙烯亚胺-SMCC-TAT/DNA 纳米颗粒递送 PUMA 凋亡基因：生物物理表征和体外转染至恶性黑色素瘤细胞
DOI：
10.1166/jbn.2015.2151
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发表时间：
2015-10-01
影响因子：
2.9
通讯作者：
He, Nongyue
中科院分区：
文献类型：
--
作者：
Li, Fu;Wang, Zhifei;He, Nongyue
设计了一种基于PEI的合成基因传递系统，其中PEI与磺基琥珀酰亚胺1-4-(N-马来酰亚胺甲基)环己烷-1-羧酸酯(Sulfo-SMCC)交联，缀合反式激活转录激活剂(TAT)，产生PEI-SMCC-TAT(PST)，一种凋亡相关基因PUMA(p53上调的凋亡调节剂)的新型非病毒载体。评价。 Sulfo-SMCC是一种常用的异双功能交联剂，可溶于水，使得交联更容易，无需DMSO或氯仿等有机试剂。在最佳 N/P 比 (50:1) 下，PST/pDNA 纳米粒子的长度为 171.9 nm。与单个PEI载体相比，所有PST缀合的DNA复合物的毒性低得多，并且转染效率提高。结果还表明，PST/pEGFP纳米粒子转染恶性黑色素瘤A375细胞的效率增加，且携带PUMA基因的PST诱导A375细胞凋亡。表明PST可能是一种有前途的黑色素瘤肿瘤靶向纳米载体，并具有良好的临床应用潜力。
A synthesized PEI-based gene delivery system, wherein PEI was crosslinked with sulfosuccinimidy1-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC) conjugating trans-activating transcriptional activator (TAT), yielding PEI-SMCC-TAT (PST), a novel non-viral vector for apoptosis-related gene PUMA (p53 up regulated modulator of apoptosis), was designed and evaluated. Sulfo-SMCC is a commonly used heterobifunctional crosslinker and is soluble in water, making the crosslinking easier without organic reagent like DMSO or chloroform. The PST/pDNA nanoparticles were 171.9 nm at the optimal N/P ratio (50:1). DNA complexes of all the PST conjugation had much lower toxicity and exhibited enhancement in transfection efficiency in comparison with single PEI vector. The results also showed that the transfection efficiency of PST/pEGFP nanoparticles into malignant melanoma A375 cell increased, and PST carrying PUMA gene induced the apoptosis of A375 cells. It was suggested that PST could be a promising melanoma tumor-targeting nanovector, and have a good potential in clinical application.