Combination of nanogel polyethylene glycol-polyethylenimine and 6(hydroxymethyl)-1,4-anthracenedione as an anticancer nanomedicine.
Combination of nanogel polyethylene glycol-polyethylenimine and 6(hydroxymethyl)-1,4-anthracenedione as an anticancer nanomedicine.
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纳米凝胶聚乙二醇-聚乙烯亚胺和6(羟甲基)-1,4-蒽二酮的组合作为抗癌纳米药物。
DOI：
10.1166/jnn.2008.294
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发表时间：
2008
影响因子：
--
通讯作者：
Troyer,Deryl
中科院分区：
文献类型：
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作者：
Ganta,Chanran;Shi,Aibin;Battina,SrinivasK;Pyle,Marla;Rana,Sandeep;Hua,DuyH;Tamura,Masaaki;Troyer,Deryl
聚乙二醇聚乙烯亚胺(PEG-PEI)纳米凝胶已被用于将核酸和寡核苷酸输送到细胞中。首先，我们合成了亚甲基质子比(CH2O：CH2N)在∼6.8：1~4：1及以下的聚乙二醇-聚乙二醇胺纳米凝胶。我们首先合成了不同比例的CH2O：CH2N(亚甲基质子)的纳米凝胶，如1H核磁共振波谱所示，并用啮齿动物胰腺癌细胞株(Pan02)测试了它们的细胞毒性。结果表明，亚甲基质子比为4：1的聚乙二醇-聚乙二醇胺纳米凝胶在体外对PAN-02细胞有较强的细胞毒作用，而亚甲基质子比为6.8：1的纳米凝胶无毒。我们将新型抗癌药物6-羟甲基-1，4-蒽二酮(AQ)类似物(AQ10)引入无毒纳米凝胶PEG-PEI(AQ10-Nanogel PEG-PEI)中，并检测了AQ10负载的纳米凝胶PEG-PEI(AQ10-Nanogel PEG-PEI)和溶解于DMSO的AQ10对Pan02细胞生长的影响。用原子力显微镜(AFM)对AQ10-纳米凝胶的尺寸进行了表征。我们的研究表明，AQ10-纳米凝胶PEI很容易被Pan02细胞摄取。AQ10纳米凝胶的细胞生长抑制作用是溶解于DMSO的AQ10细胞的3~4倍。这些结果表明，通常用于将核酸输送到细胞内的PEG-PEI也可以用于输送不溶性小分子抗癌药物AQ10。
Polyethylene glycol-polyethylenimine (PEG-PEI) nanogels have been used to deliver nucleic acids and oligonucleotides into cells. First, we synthesized PEG-PEI nanogels with methylene proton ratios (CH2O:CH2N) in PEG-PEI ranging from ∼6.8:1 to 4:1 and less, as shown by 1H NMR spectra. We first synthesized various nanogels with varying ratios of CH2O:CH2N (methylene proton) in PEG-PEI as shown by 1H NMR spectra and tested their cytotoxicity using a rodent pancreatic adenocarcinoma cell line (Pan 02). We showed that the nanogel PEG-PEI with methylene proton ratio of 4:1 was strongly cytotoxic to Pan 02 cells in vitro, while the nanogel with the methylene proton ratio of 6.8:1 was not toxic. We incorporated a novel anti-cancer drug, 6-(hydroxymethyl)-1,4-anthracenedione (AQ) analogue (AQ10) into nontoxic nanogel PEG-PEI and tested the effect of AQ10 loaded nanogel PEG-PEI (AQ10-nanogel PEG-PEI) and AQ10 dissolved in DMSO on Pan 02 cell growth. The size of this AQ10-nanogel PEG-PEI was characterized using atomic force microscopy (AFM). Our studies showed that the AQ10-nanogel PEG-PEI is readily taken up by Pan 02 cells. Growth attenuation of Pan 02 cells treated with AQ10-nanogel PEG-PEI was three to four times that of cells treated with AQ10 dissolved in DMSO. These results suggest that PEG-PEI, usually used to deliver nucleic acids into cells, can also be used to deliver an insoluble small molecule anticancer drug, AQ10.