Department of Chemical, Biological & Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700106, India.
Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Salt Lake, Kolkata 700106, India.
ACS Appl Bio Mater. 2021 Dec 20;4(12):8259-8266. doi: 10.1021/acsabm.1c00804. Epub 2021 Nov 9.
To realize a customizable biogenic delivery platform, herein we propose combining cell-derived extracellular vesicles (EVs) derived from breast cancer cell line MCF-7 with synthetic cationic liposomes using a fusogenic agent, polyethylene glycol (PEG). We performed a fluorescence resonance energy transfer (FRET)-based lipid-mixing assay with varying PEG 1000 concentrations (0%, 15%, and 30%) correlated with flow cytometry-based analysis and supported by dimensional analysis by dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) to validate our fusion strategy. Our data revealed that these hybrid vesicles at a particular concentration of PEG (∼15%) improved the cellular delivery efficiency of a model siRNA molecule to the EV parental breast cancer cells, MCF-7, by factors of 2 and 4 compared to the loaded liposome and EV precursors, respectively. The critical rigidity/pliability balance of the hybrid systems fused by PEG seems to be playing a pivotal role in improving their delivery capability. This approach can provide clinically viable delivery solutions using EVs.
为了实现可定制的生物衍生递药平台，我们在此提出将乳腺癌细胞系 MCF-7 来源的细胞外囊泡（EVs）与合成阳离子脂质体通过融合试剂聚乙二醇（PEG）结合起来。我们进行了基于荧光共振能量转移（FRET）的脂质混合测定，改变 PEG1000 浓度（0%、15%和 30%），并结合流式细胞术分析，同时通过动态光散射（DLS）、透射电子显微镜（TEM）和原子力显微镜（AFM）进行了维度分析，以验证我们的融合策略。我们的数据表明，在特定 PEG 浓度（约 15%）下，这些杂交囊泡可分别将模型 siRNA 分子递送至 EV 亲本乳腺癌细胞 MCF-7 的细胞内递送效率提高 2 倍和 4 倍，与负载脂质体和 EV 前体相比。PEG 融合的杂交系统的临界刚性/柔韧性平衡似乎在提高其递药能力方面发挥着关键作用。这种方法可以使用 EV 提供临床可行的递药解决方案。
