Zhang Wei, Ngo Long, Tsao Simon Chang-Hao, Liu Dingbin, Wang Yuling
ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW 2109, Australia.
School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
ACS Appl Mater Interfaces. 2023 Apr 5;15(13):16420-16433. doi: 10.1021/acsami.2c22749. Epub 2023 Mar 24.
Cancer-derived small extracellular vesicles (sEVs) may be a promising drug delivery system that targets cancer cells due to their unique features, such as native homing ability, biological barrier crossing capability, and low immune response. However, the oncogenic cargos within them pose safety concerns, hence limiting their application thus far. We proposed using an electroporation-based strategy to extract the endogenous cargos from cancer-derived sEVs and demonstrated that their homing ability was still retained. A membrane fusion technique was used to fuse these sEVs with liposomes to form hybrid particles, which possessed both benefits of sEVs and liposomes. Anti-EGFR monoclonal antibodies were modified on the hybrid particles to improve their targeting ability further. The engineered hybrid particles showed higher drug loading ability that is 33.75 and 43.88% higher than that of liposomes and sEVs, respectively, and improved targeting ability by 52.23% higher than hybrid particles without modification. This delivery system showed >90% cell viability and enhanced treatment efficiency with 91.58 and 79.26% cell migration inhibition rates for the miR-21 inhibitor and gemcitabine, respectively.
癌症衍生的小细胞外囊泡（sEVs）可能是一种很有前景的靶向癌细胞的药物递送系统，因为它们具有独特的特性，如天然归巢能力、跨越生物屏障的能力和低免疫反应。然而，其中的致癌货物引发了安全问题，因此限制了它们目前的应用。我们提出使用基于电穿孔的策略从癌症衍生的sEVs中提取内源性货物，并证明它们的归巢能力仍然保留。采用膜融合技术将这些sEVs与脂质体融合形成杂合颗粒，其兼具sEVs和脂质体的优点。在杂合颗粒上修饰抗表皮生长因子受体（EGFR）单克隆抗体以进一步提高其靶向能力。工程化的杂合颗粒显示出更高的载药能力，分别比脂质体和sEVs高33.75%和43.88%，并且靶向能力比未修饰的杂合颗粒提高了52.23%。这种递送系统显示出>90%的细胞活力，对于miR-21抑制剂和吉西他滨，细胞迁移抑制率分别为91.58%和79.26%，提高了治疗效率。
