Investigation of water-insoluble hydrophobic polyethylenimines as RNAi vehicles in chronic myeloid leukemia therapy

J Biomed Mater Res A. 2021 May 8. doi: 10.1002/jbm.a.37214. Online ahead of print.ABSTRACTThe discovery of RNA interference (RNAi) more than two decades ago opened avenues for avant-garde cancer treatments that possess the ability to evade issues hampering current chemotherapeutic strategies, owing to its specific gene sequence-driven mechanism of action. A potent short interfering RNA (siRNA) delivery vehicle designed to overcome physiological barriers is imperative for successful RNAi therapy. For this purpose, this study explored the characteristics and therapeutic efficacy of low-molecular weight (MW) polyethylenimine (PEI) with high cholesterol substitution, yielding water-insoluble polymers, in chronic myeloid leukemia (CML) K562 cells. A strong impact of cholesterol grafting on the physicochemical attributes of the resultant polymers and their corresponding complexes with siRNA was observed, with the siRNA binding capacity of polymers increasing and complex dissociation sensitivity decreasing with increase in cholesterol content of the polymers. The modified polymer complexes were significantly smaller in size and possessed higher cationic charge compared to the parent polymer. The interaction with anionic heparan sulfate preoteoglycans present on the cell surface was significant in cellular uptake of the complexes. The therapeutic efficacy of siRNA/polymer complexes was reflected in their ability to effectively silence the reporter green fluorescent protein gene and e...
Source: Biomed Res - Category: Research Authors: Source Type: research

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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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This article is protected by copyright. All rights reserved. PMID: 31714657 [PubMed - as supplied by publisher]
Source: Biomed Res - Category: Research Authors: Tags: J Biomed Mater Res A Source Type: research
This study included 18 buffy coats collected from volunteer blood donors admitted to the blood transfusion service of IRCCS Bambino Gesù Pediatric Hospital after obtaining informed consent. The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014) and conducted in accordance with the ethical principles stated in the Declaration of Helsinki. Cells Lines and Cell Culture NK-92 (malignant non-Hodgkin's lymphoma), K562 (chronic myelogenous leukemia, CD19−), Jurkat (acute T cell leukemia, CD19−) Karpas 299 (Human Non-Hodgkin's Ki-positive Large Cell ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Bipolar Disorder Current Issue Drug Development Mental Disorders Mood Disorders Original Research Psychiatry Psychopharmacology disease burden expenditures major depressive disorder pharmaceutical innovation research and developmen Source Type: research
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Source: Journal of Proteomics - Category: Biochemistry Authors: Tags: J Proteomics Source Type: research
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