Active transfection of genetic materials using cyclodextrin-anchored nanovectors

IF 5.2 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY
Amey Revdekar, Bhagyashree V. Salvi and Pravin Shende
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Abstract

Gene-based therapy is a sophisticated means for the treatment of various complex diseases like AIDS, cancer, etc., as it resolves the genetic malfunction at the source instead of tackling the superficial symptoms. However, the therapeutic, diagnostic, and theranostic potential of gene-based therapeutic actives such as siRNA, mRNA, pDNA, aptamers, etc. is hindered by physicochemical as well as physiological barriers in the form of insufficient bioavailability, systemic metabolism, rapid renal clearance, inefficient carrier systems, etc. Although advanced carrier systems such as polyplexes, lipoplexes, dendriplexes, hydrogels, polyrotaxanes, etc. are employed to overcome such challenges, their structural configuration results in notable cytotoxicity to induce bio-incompatibility. In this context, strategic integration of cyclodextrins subdues the cytotoxicity by virtue of unique architectural characteristics and allows the fabrication of sophisticated systems for delivery of gene-based therapeutics. Inclusion of cyclodextrins offers benefits like enhanced protection of gene-targeted payloads, compact loading, nanoscale carrier dimensions, biostability, etc. by forming densely packed cargo systems. Cyclodextrins nullify the active cationic moieties to lower in vivo cytotoxicity and improve transfection efficiency across biomembranes. The multi-ligand binding capability of structurally-modulated cyclodextrins avails receptor specificity and gene-targeted therapeutic efficiency. The ability to form reversible covalent linkages allows the fashioning of multi-stimuli responsive supramolecular nanocarriers for a desirable drug release profile. The present review article features cyclodextrins and associated successful applications as the integral components of non-viral nanovectors such as cationic polymers, dendrimers and polyrotaxanes as well as supramolecular assemblies for efficient delivery of RNA-, DNA- and aptamer-based genetic payloads for the achievement of desired treatment outcomes.

Abstract Image

利用环糊精锚定纳米载体主动转染遗传物质
基因疗法是治疗艾滋病、癌症等各种复杂疾病的一种复杂手段,因为它从源头上解决基因故障,而不是解决表面症状。然而,基于基因的治疗活性物质如siRNA、mRNA、pDNA、适体等的治疗、诊断和治疗潜力受到物理化学和生理障碍的阻碍,这些障碍表现为生物利用度不足、全身代谢、肾脏清除迅速、载体系统效率低下等。虽然先进的载体体系如多聚体、脂丛、树突丛、水凝胶、聚轮烷等被用来克服这些挑战,但它们的结构配置导致显著的细胞毒性,诱导生物不相容。在这种情况下,环糊精的战略性整合凭借其独特的结构特征降低了细胞毒性,并允许制造复杂的系统来提供基于基因的治疗方法。环糊精的加入通过形成密集的货物系统,增强了对基因靶向有效载荷的保护、紧凑的装载、纳米级载体尺寸、生物稳定性等方面的好处。环糊精使活性阳离子部分无效,降低体内细胞毒性,提高跨生物膜的转染效率。结构调节的环糊精具有多配体结合能力,具有受体特异性和基因靶向治疗效果。形成可逆共价键的能力允许形成多刺激反应的超分子纳米载体,以获得理想的药物释放谱。本综述介绍了环糊精和相关的成功应用,作为非病毒纳米载体的组成部分,如阳离子聚合物、树状大分子和聚轮烷,以及用于高效递送RNA、DNA和基于适体的遗传有效载荷的超分子组件,以实现预期的治疗效果。
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
Materials Advances
Materials Advances MATERIALS SCIENCE, MULTIDISCIPLINARY-
CiteScore
7.60
自引率
2.00%
发文量
665
审稿时长
5 weeks
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