Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Vera Vysochinskaya , Yana Zabrodskaya , Olesya Dovbysh , Anton Emelyanov , Vladimir Klimenko , Nikolay Knyazev , Ivan Terterov , Marya Egorova , Alexey Bogdanov , Michael Maslov , Andrey Vasin , Michael Dubina
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引用次数: 0

Abstract

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL1, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model.

The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2Х3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2Х3-DOPE-DSPE-PEG2000 (0.62 % mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL1) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

细胞穿透肽和阳离子脂质体介导的 siRNA 体外递送可阻止慢性髓性白血病细胞生长
通过 RNA 干扰(RNAi)进行基因沉默是治疗包括癌症在内的多种疾病的一种很有前景的方法。鉴于临床上酪氨酸激酶抑制剂(TKIs)耐药性的普遍存在,使用针对 BCR-ABL1 的特异性 siRNA 的非病毒基因疗法可以作为传统慢性髓性白血病(CML)酪氨酸激酶抑制剂(TKIs)疗法的辅助或替代措施。这类方法面临的主要挑战仍然是开发适合特定疾病模型的 siRNA 有效递送系统。本研究的目的是考察和比较内溶解性细胞穿透肽(CPP)EB1 和由多阳离子脂质 1、26-双(胆甾-5-烯-3-氧羰基氨基)-7,11,16,20-四氮杂六氧羰基四盐酸盐(2Х3)和辅助脂质 1,2-二油酰-sn-甘油-3-磷脂乙醇胺(DOPE)组成的阳离子脂质体向 K562 人 CML 细胞系递送抗-bcr-abl siRNA 的效率。我们的研究表明,EB1 和 2Х3-DOPE-DSPE-PEG2000 (0.62% mol.)脂质体都能通过内吞机制将 siRNA 有效地递送到 K562 细胞中,而且使用脂质体能更有效地抑制靶基因(BCR-ABL1)的表达和癌细胞的增殖。综上所述,这些研究结果表明,PEG修饰的阳离子脂质体介导的siRNA递送能有效地反义抑制某些癌基因,是一种很有前景的治疗慢性骨髓性白血病的新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochimie
Biochimie 生物-生化与分子生物学
CiteScore
7.20
自引率
2.60%
发文量
219
审稿时长
40 days
期刊介绍: Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English. Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.
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