Chen Hao, Ding Qiaojiao, Li Lin, Wei Pengyao, Niu Zitong, Kong Tong, Fu Pan, Wang Yuhui, Li Jiang, Wang Kaizhe, Zheng Jianping
Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315300, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
JACS Au. 2024 May 30;4(6):2381-2392. doi: 10.1021/jacsau.4c00338. eCollection 2024 Jun 24.
Extracellular vesicles (EVs) are naturally occurring vesicles secreted by cells that can transport cargo between cells, making them promising bioactive nanomaterials. However, due to the complex and heterogeneous biological characteristics, a method for robust EV manipulation and efficient EV delivery is still lacking. Here, we developed a novel class of extracellular vesicle spherical nucleic acid (EV-SNA) nanostructures with scalability, programmability, and efficient cellular delivery. EV-SNA was constructed through the simple hydrophobic coassembly of natural EVs with cholesterol-modified oligonucleotides and can be stable for 1 month at room temperature. Based on programmable nucleic acid shells, EV-SNA can respond to AND logic gates to achieve vesicle assembly manipulation. Importantly, EV-SNA can be constructed from a wide range of biological sources EV, enhancing cellular delivery capability by nearly 10-20 times. Compared to artificial liposomal SNA, endogenous EV-SNA exhibited better biocompatibility and more effective delivery of antisense oligonucleotides in hard-to-transfect primary stem cells. Additionally, EV-SNA can deliver functional EVs for immune regulation. As a novel material form, EV-SNA may provide a modular and programmable framework paradigm for EV-based applications in drug delivery, disease treatment, nanovaccines, and other fields.
细胞外囊泡(EVs)是细胞自然分泌的囊泡,能够在细胞间运输物质,使其成为很有前景的生物活性纳米材料。然而,由于其复杂且异质的生物学特性,目前仍缺乏一种强大的EV操作方法和高效的EV递送方法。在此,我们开发了一类新型的细胞外囊泡球形核酸(EV-SNA)纳米结构,具有可扩展性、可编程性和高效的细胞递送能力。EV-SNA通过天然EV与胆固醇修饰的寡核苷酸简单的疏水共组装构建而成,在室温下可稳定保存1个月。基于可编程的核酸外壳,EV-SNA能够响应“与”逻辑门以实现囊泡组装操作。重要的是,EV-SNA可以由多种生物来源的EV构建而成,将细胞递送能力提高了近10到20倍。与人工脂质体SNA相比,内源性EV-SNA在难以转染的原代干细胞中表现出更好的生物相容性和更有效的反义寡核苷酸递送效果。此外,EV-SNA可以递送功能性EV用于免疫调节。作为一种新型材料形式,EV-SNA可能为基于EV的药物递送、疾病治疗、纳米疫苗及其他领域的应用提供一个模块化和可编程的框架范例。