Development of Functional Chimeric Nanoparticles by Membrane Fusion of Small Extracellular Vesicles and Drug-Encapsulated Liposomes.
Development of Functional Chimeric Nanoparticles by Membrane Fusion of Small Extracellular Vesicles and Drug-Encapsulated Liposomes.
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通过小细胞外囊泡和药物封装脂质体的膜融合开发功能性嵌合纳米颗粒。
DOI：
10.1248/bpb.b23-00135
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发表时间：
2023
影响因子：
2
通讯作者：
K. Kogure
中科院分区：
文献类型：
--
作者：
T. Fukuta;Akina Nishikawa;Ami Hiramachi;Sachika Yamashita;K. Kogure
由于小细胞外囊泡（sEV）通过某些生物活性分子的转移参与细胞与细胞的通信，并且具有克服针对药物转运的生物屏障的能力，因此它们作为药物递送系统（DDS）的用途已经在多种疾病的治疗中得到证实。然而，药物包封中的一些问题已被指出，包括包封率低和重现性差。先前报道，含有磷脂酰丝氨酸（PS）的脂质体可以在钙离子存在下融合在一起，这允许药物包封到所得脂质体中（即，钙熔融法）。另一方面，据报道PS作为独特的脂质组成存在于sEV的脂质膜中。因此，我们假设通过钙融合方法将sEV与包封治疗剂的PS-脂质体的PS-介导的膜融合可用于方便地将药物包封到sEV中。首次证实了PS-脂质体与小鼠黑色素瘤B16 F1细胞来源的sEVs（B16-sEVs）的膜融合。所获得的称为嵌合纳米颗粒（CM-NP）的纳米颗粒显示出与B16-sEV相当的细胞摄取到B16 F1细胞中。此外，包封抗癌药物阿霉素（DOX）的CM-NP（CM-NP-DOX）可以通过包封DOX的PS-脂质体（PS-Lipo-DOX）和B16-sEV的膜融合来制备。CM-NP-DOX在体外对B16 F1细胞的抗癌作用优于PS-Lipo-DOX。这些发现表明，钙融合方法可以应用于sEV和PS-脂质体的膜融合，并且这种方法可能有助于有效地将药物包封到sEV中，以及增加脂质体功能。
Since small extracellular vesicle (sEVs) are involved in cell-to-cell communication via transfer of certain bioactive molecules and have the capability to overcome biological barriers against drug transport, their use as a drug delivery system (DDS) has been demonstrated in treatment of a diverse range of diseases. However, some issues in drug encapsulation have been pointed out, including low encapsulation efficiency and poor reproducibility. It was previously reported that liposomes containing phosphatidylserine (PS) can fuse together in the presence of calcium ion, which allows for drug encapsulation into the resultant liposomes (i.e., calcium fusion method). On the other hand, PS is reportedly present in lipid membrane of sEVs as a distinct lipid composition. We therefore hypothesized that PS-mediated membrane fusion of sEVs with PS-liposomes encapsulating therapeutic agents via the calcium fusion method can be applied to convenient drug encapsulation into sEVs. Membrane fusion of PS-liposomes and sEVs derived from murine melanoma B16F1 cells (B16-sEVs) was firstly confirmed. The obtained nanoparticles, termed chimeric nanoparticles (CM-NP), showed comparable cellular uptake to B16-sEVs into B16F1 cells. Moreover, CM-NP encapsulating an anticancer drug doxorubicin (DOX) (CM-NP-DOX) could be prepared by membrane fusion of PS-liposomes encapsulating DOX (PS-Lipo-DOX) and B16-sEVs. CM-NP-DOX exhibited a superior anticancer effect on B16F1 cells in vitro compared with PS-Lipo-DOX. These findings suggest that the calcium fusion method could be applied for membrane fusion of sEVs and PS-liposomes, and that this approach would likely be useful for efficient drug encapsulation into sEVs, as well as increasing liposome functionality.