α-Tocopherol-anchored gemini lipids with delocalizable cationic head groups: the effect of spacer length on DNA compaction and transfection properties.

作者: Srilakshmi V Patri , Mallikarjun Gosangi , Hithavani Rapaka , Venkatesh Ravula

DOI: 10.1039/D1OB00475A

关键词:

摘要: Understanding the role of structural units in cationic lipids used for gene delivery is essential designing efficient vehicles. Herein, we report a systematic structure–activity investigation on influence spacer length DNA compaction ability and transfection properties gemini with delocalizable head groups. We have synthesized series dimeric varying length. The binding interactions liposomal formulations were characterized by gel electrophoresis ethidium bromide (EtBr) exclusion assays. Condensation potentials optimized best results observed possessing 6 methylene (TIM 6). found that size lipid/DNA complex decreased increase chain up to TIM increased further. lipid/DOPE molar formulation using β-galactosidase activity assay ratio 1 : 1.5 (gemini lipid/DOPE) showed maximum among all ratios. cellular uptake co-localization lipoplexes cell analysis imaging confocal microscopy. confirm lipoplex derived from lipid pCMV-bgal/DNA internalizes via endocytosis. cytotoxicity studies MTT revealed show comparable viability commercial standard even at higher charge Overall, data suggest these dimers depends containing six aliphatic has potential deliver genes.

参考文章(40)
Sang Myoung Noh, Su Eun Han, Gayong Shim, Kyoung Eun Lee, Chan-Wha Kim, Sung Sik Han, Yongseok Choi, Young Keun Kim, Won-Ki Kim, Yu-Kyoung Oh, Tocopheryl oligochitosan-based self assembling oligomersomes for siRNA delivery Biomaterials. ,vol. 32, pp. 849- 857 ,(2011) , 10.1016/J.BIOMATERIALS.2010.09.027
E Dodds, MG Dunckley, K Naujoks, U Michaelis, G Dickson, Lipofection of cultured mouse muscle cells: a direct comparison of Lipofectamine and DOSPER. Gene Therapy. ,vol. 5, pp. 542- 551 ,(1998) , 10.1038/SJ.GT.3300604
Voshavar Chandrashekhar, Marepally Srujan, Rairala Prabhakar, Rakesh C Reddy, Bojja Sreedhar, Kiran KR Rentam, Sanjit Kanjilal, Arabinda Chaudhuri, None, Cationic amphiphiles with fatty acyl chain asymmetry of coconut oil deliver genes selectively to mouse lung. Bioconjugate Chemistry. ,vol. 22, pp. 497- 509 ,(2011) , 10.1021/BC100537R
Santanu Bhattacharya, Avinash Bajaj, Advances in gene delivery through molecular design of cationic lipids Chemical Communications. pp. 4632- 4656 ,(2009) , 10.1039/B900666B
Yoshitaka Uno, Wenying Piao, Kanjiro Miyata, Kazutaka Nishina, Hidehiro Mizusawa, Takanori Yokota, High-Density Lipoprotein Facilitates In Vivo Delivery of α-Tocopherol–Conjugated Short-Interfering RNA to the Brain Human Gene Therapy. ,vol. 22, pp. 711- 719 ,(2011) , 10.1089/HUM.2010.083
Krishan Kumar, Bappa Maiti, Paturu Kondaiah, Santanu Bhattacharya, Efficacious Gene Silencing in Serum and Significant Apoptotic Activity Induction by Survivin Downregulation Mediated by New Cationic Gemini Tocopheryl Lipids Molecular Pharmaceutics. ,vol. 12, pp. 351- 361 ,(2015) , 10.1021/MP500620E
Inge S Zuhorn, Willy H Visser, Udo Bakowsky, Jan B.F.N Engberts, Dick Hoekstra, Interference of serum with lipoplex-cell interaction: modulation of intracellular processing. Biochimica et Biophysica Acta. ,vol. 1560, pp. 25- 36 ,(2002) , 10.1016/S0005-2736(01)00448-5
Avinash Bajaj, Paturu Kondaiah, Santanu Bhattacharya, Synthesis and gene transfer activities of novel serum compatible cholesterol-based gemini lipids possessing oxyethylene-type spacers. Bioconjugate Chemistry. ,vol. 18, pp. 1537- 1546 ,(2007) , 10.1021/BC070010Q
Hongtao Lv, Shubiao Zhang, Bing Wang, Shaohui Cui, Jie Yan, Toxicity of cationic lipids and cationic polymers in gene delivery. Journal of Controlled Release. ,vol. 114, pp. 100- 109 ,(2006) , 10.1016/J.JCONREL.2006.04.014
Shinichi Mochizuki, Naho Kanegae, Koichi Nishina, Yumi Kamikawa, Kazunori Koiwai, Hiroyasu Masunaga, Kazuo Sakurai, The role of the helper lipid dioleoylphosphatidylethanolamine (DOPE) for DNA transfection cooperating with a cationic lipid bearing ethylenediamine Biochimica et Biophysica Acta. ,vol. 1828, pp. 412- 418 ,(2013) , 10.1016/J.BBAMEM.2012.10.017