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In this study, we designed highly hydrophobic cationic lipopolymers by grafting cholesterol (Chol) onto low\u2010molecular weight (0.6, 1.2, and 2.0 kDa) polyethylenimines (PEIs) to enable specific siRNA therapy to chronic myeloid leukemia (CML) cells. The siRNA binding by PEI\u2010Chol led to nano\u2010sized (100\u2013200\u2009nm diameter) polyplexes with enhanced \u03b6\u2010potential (+20 to +35\u2009mV) and ability to protect the loaded siRNA completely in fresh serum. The siRNA delivery to CML (K562) cells was proportional to degree of substitution and, unexpectedly, inversely proportional to molecular size of the polymeric backbone. Chol grafting with as little as ~1.0 Chol\/PEI on 0.6 and 1.2 kDa PEIs enabled silencing of the reporter Green Fluorescent Protein gene as well as the endogenous BCR\u2010Abl oncogene in K562 cells. The PEI\u2010Chol mediated delivery of siRNAs specific for BCR\u2010Abl and KSP genes significantly arrested the growth the cells which was significantly reflected in colony formation potency of K562 cells. BCR\u2010Able siRNA mediated therapeutic efficacy was also observed in significantly increased caspase activity and apoptosis of K562 cells. Thus, Chol\u2010grafted low\u2010molecular weight PEIs appear to be unique siRNA carriers to realize the molecular therapy in CML cells.<\/jats:p>","DOI":"10.1002\/jbm.a.36837","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T16:57:06Z","timestamp":1573577826000},"page":"565-580","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cholesterol grafted cationic lipopolymers: Potential siRNA carriers for selective chronic myeloid leukemia therapy"],"prefix":"10.1002","volume":"108","author":[{"given":"KC","family":"Remant","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Material Engineering, Faculty of Engineering University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Thapa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Valencia\u2010Serna","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj S.","family":"Domun","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Material Engineering, Faculty of Engineering University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailean","family":"Dimitroff","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Material Engineering, Faculty of Engineering University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of 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