RNA Encapsulation in Metal–Organic Frameworks for Targeting Cancer-Causing Genes

IF 3.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY Advanced Therapeutics Pub Date : 2024-07-18 DOI:10.1002/adtp.202400144
Meemansha Mishra, Tapan Dey, Mallya Mishra, Isha Chauhan, Saikat Dutta
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Abstract

A rapid emergence of small interfering ribonucleic acid (siRNA) is witnessed as a powerful tool in gene therapy for suppressing gene expression. Since highly porous metal-organic frameworks (MOFs) are fragile and inefficient with non-specific gene delivery techniques, developing strategies use them to encapsulate unmodified natural siRNA from enzymatic degradation. MOFs with high nucleic acid binding affinity are ideal for encapsulating siRNAs in cancer therapy, bypassing circulation time and non-specificity. To knock down Plk1gene, tumor cell membranes can hide Plk1 siRNA-containing (Zeolitic Imidazolate framework) ZIF-8 nanoparticles. For tumor suppression MOF-promoted lysosome siRNA release, cell membrane coating, and PLK1 silencing are employed. Lysosomes attack cancer by delivering miRNA to targeted cells. Single-stranded miRNA, two-stranded siRNA. Despite their different sources, structures, modes of action, and biological activities, miRNA and siRNA regulate gene expression. SIRNA blocks genes more accurately than miRNA, which regulates larger genes. SiRNA-MOF integration in vitro results in a maximum of 27% consistent gene silencing during endocytic absorption. Cofactor-encapsulated MOF-internalized siRNA kills enzymes. A universal siRNA delivery for a specific genetic sequence with personalized therapeutic potential contrasts with multi-route cancer drugs. SiRNAs cleave long-stranded RNAs coding for specific genes, allowing biocompatible MOFs to encapsulate macromolecules and protect them from injury.

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在金属有机框架中封装 RNA 以靶向致癌基因
小干扰核糖核酸(siRNA)作为一种抑制基因表达的强大工具在基因治疗领域迅速崛起。由于高多孔金属有机框架(MOFs)在非特异性基因递送技术中易碎且效率低下,因此开发战略利用它们来封装未经修饰的天然 siRNA,以防止酶降解。具有高核酸结合亲和力的 MOFs 是在癌症治疗中封装 siRNA 的理想选择,可绕过循环时间和非特异性。为了敲除 Plk1 基因,肿瘤细胞膜可以隐藏含有 Plk1 siRNA 的(沸石咪唑啉框架)ZIF-8 纳米粒子。为了抑制肿瘤,采用了 MOF 促进溶酶体 siRNA 释放、细胞膜包裹和 PLK1 沉默的方法。溶酶体通过向目标细胞输送 miRNA 来攻击癌症。单链 miRNA、双链 siRNA。尽管 miRNA 和 siRNA 的来源、结构、作用方式和生物活性各不相同,但它们都能调节基因表达。与调控较大基因的 miRNA 相比,siRNA 能更准确地阻断基因。SiRNA-MOF 在体外整合时,内吞吸收过程中基因沉默的一致性最高可达 27%。辅助因子封装的 MOF 内置 siRNA 可杀死酶。针对特定基因序列的通用 siRNA 输送具有个性化治疗潜力,与多途径抗癌药物形成鲜明对比。SiRNA 可裂解编码特定基因的长链 RNA,使生物相容性 MOF 能够封装大分子并保护它们免受损伤。
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来源期刊
Advanced Therapeutics
Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.10
自引率
2.20%
发文量
130
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