Development of an innovative extracellular vesicle mimetic delivery platform for efficient miRNA delivery to tumours

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-03-20 DOI:10.1016/j.biomaterials.2025.123282

Rui Chen , Chintan Bhavsar , Rohan Lourie , Shuying Li , Sherry Y. Wu

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引用次数: 0

Abstract

Extracellular vesicles (EVs) display high degree of tissue tropism and therefore represent promising carriers for tissue-specific delivery of genes or drugs for the treatment of human diseases. However, current approaches for the loading of therapeutics into EVs have low entrapment efficiency and also do not adequately deplete endogenous EV content; thus, more effective approaches are needed. Here, we report an innovative EXtraCElluar vesicle surface Ligand-NanoParticles (EXCEL NPs), generated by transferring moieties of EVs onto the surface of synthetic nanoparticles. EXCEL NPs facilitate the efficient entrapment of therapeutics (89 % efficiency) and are completely devoid of pre-existing unwanted EV internal content. Importantly, we show that EXCEL NPs formulated using EVs derived from endothelial cells, astrocytes and macrophages retain the delivery characteristics of the original EVs. Using miRNA-146a as a model anti-cancer therapeutic, we further demonstrated successful delivery of miRNA-146a to IG10 orthotopic ovarian tumours in immune competent mice using EXCEL NPs formulated with macrophage-derived EVs. Our findings establish a new clinically translatable approach to leverage characteristics of endogenous EVs for therapeutic delivery. The versatility of the platform enables future application to different target cell types and therapeutic modalities.

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开发一种创新的细胞外囊泡模拟递送平台，用于有效地向肿瘤递送miRNA

细胞外囊泡（EVs）表现出高度的组织亲和性，因此是治疗人类疾病的组织特异性基因或药物递送的有希望的载体。然而，目前将治疗药物装入EV的方法具有较低的捕获效率，也不能充分消耗内源性EV含量；因此，需要更有效的办法。在这里，我们报告了一种创新的细胞外囊泡表面配体纳米颗粒（EXCEL NPs），通过将大部分ev转移到合成纳米颗粒表面而产生。EXCEL NPs促进了治疗药物的有效捕获（89%的效率），并且完全没有预先存在的不需要的EV内部内容。重要的是，我们发现使用内皮细胞、星形胶质细胞和巨噬细胞衍生的ev配制的EXCEL NPs保留了原始ev的递送特性。利用miRNA-146a作为抗癌治疗模型，我们进一步证明了使用巨噬细胞来源的ev配制的EXCEL NPs成功地将miRNA-146a递送到免疫功能小鼠的IG10原位卵巢肿瘤。我们的研究结果建立了一种新的临床可翻译的方法来利用内源性ev的特性进行治疗递送。该平台的多功能性使未来应用于不同的靶细胞类型和治疗方式。

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

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.