AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells.

作者: Diana Rafael , Petra Gener , Fernanda Andrade , Joaquin Seras-Franzoso , Sara Montero

DOI: 10.1080/10717544.2018.1461276

关键词: PolyethylenimineAKT2CarcinogenesisGene deliveryChemistryOncogeneCancer stem cellRNA interferenceCancer researchGene silencing

摘要: Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible sustaining the metastatic spread disease to distal organs and progressive gain resistance cancers, new anticancer should be validated specifically this subpopulation cells. A amphihilic-based gene delivery system that combines Pluronic® F127 micelles polyplexes spontaneously formed by electrostatic interaction between anionic siRNA cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather requirements an efficient safe transport in terms its physicochemical characteristics, internalization capacity, toxicity profile silencing efficacy. were loaded against AKT2, important oncogene involved breast tumorigenesis, special role CSC malignancy. Efficacy siAKT2-PM isol...

参考文章(58)
Arun K. Iyer, Zhenfeng Duan, Mansoor M. Amiji, Nanodelivery systems for nucleic acid therapeutics in drug resistant tumors. Molecular Pharmaceutics. ,vol. 11, pp. 2511- 2526 ,(2014) , 10.1021/MP500024P
Chann Lagadec, Erina Vlashi, Lorenza Della Donna, YongHong Meng, Carmen Dekmezian, Kwanghee Kim, Frank Pajonk, Survival and self-renewing capacity of breast cancer initiating cells during fractionated radiation treatment. Breast Cancer Research. ,vol. 12, pp. 1- 13 ,(2010) , 10.1186/BCR2479
Yining Lin, Paschalis Alexandridis, Temperature-Dependent Adsorption of Pluronic F127 Block Copolymers onto Carbon Black Particles Dispersed in Aqueous Media Journal of Physical Chemistry B. ,vol. 106, pp. 10834- 10844 ,(2002) , 10.1021/JP014221I
Achim Aigner, Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo. BioMed Research International. ,vol. 2006, pp. 71659- 71659 ,(2006) , 10.1155/JBB/2006/71659
Grace Ramena, Randolph C Elble, Yang Yu, The role of cancer stem cells in relapse of solid tumors. Frontiers in Bioscience. ,vol. 4, pp. 1528- 1541 ,(2012) , 10.2741/478
Zhihui Yang, Gaurav Sahay, Srikanth Sriadibhatla, Alexander V. Kabanov, Amphiphilic Block Copolymers Enhance Cellular Uptake and Nuclear Entry of Polyplex-Delivered DNA Bioconjugate Chemistry. ,vol. 19, pp. 1987- 1994 ,(2008) , 10.1021/BC800144A
Yan Deng, Chi Chiu Wang, Kwong Wai Choy, Quan Du, Jiao Chen, Qin Wang, Lu Li, Tony Kwok Hung Chung, Tao Tang, None, Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies. Gene. ,vol. 538, pp. 217- 227 ,(2014) , 10.1016/J.GENE.2013.12.019
Tatiana Demina, Irina Grozdova, Oxana Krylova, Artem Zhirnov, Vladislav Istratov, Holger Frey, Holger Kautz, Nikolay Melik-Nubarov, Relationship between the structure of amphiphilic copolymers and their ability to disturb lipid bilayers. Biochemistry. ,vol. 44, pp. 4042- 4054 ,(2005) , 10.1021/BI048373Q
Yuting Wen, Shirong Pan, Xin Luo, Wei Zhang, Yuan Shen, Min Feng, None, PEG- and PDMAEG-Graft-Modified Branched PEI as Novel Gene Vector: Synthesis, Characterization and Gene Transfection Journal of Biomaterials Science-polymer Edition. ,vol. 21, pp. 1103- 1126 ,(2010) , 10.1163/092050609X12459295750316