Salem Dina, Abdel-Ghany Shaimaa, Mohamed Eman, Alahmady Nada F, Alqosaibi Amany, Al-Dhuayan Ibtesam S, Alnamshan Mashal Meshal, Arneth Rebekka, Arneth Borros, Sabit Hussein
Department of Agriculture Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt.
Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt.
Pharmaceuticals (Basel). 2025 Jun 4;18(6):844. doi: 10.3390/ph18060844.
: Exosomes have recently attracted significant attention for their potential in drug delivery. Plant-derived exosomes, in particular, may serve as direct anticancer agents due to their unique characteristics, including immunogenicity, biocompatibility, safety, cell-free nature, and nanoscale structure. : This study characterizes (avocado)-derived exosomes, exploring their anticancer properties, proteomic profile, and therapeutic potential. : Isolated exosomes exhibited a diameter of 99.58 ± 5.09 nm (non-loaded) and 151.2 ± 6.36 nm (doxorubicin (DOX)-loaded), with zeta potentials of -17 mV and -28 mV, respectively. Proteomic analysis identified 47 proteins, including conserved exosome markers (GAPDH, tubulin) and stress-response proteins (defensin, endochitinase). Functional enrichment revealed roles in photosynthesis, glycolysis, ATP synthesis, and transmembrane transport, supported by protein-protein interaction networks highlighting energy metabolism and cellular trafficking. DOX encapsulation efficiency was 18%, with sustained release (44.4% at 24 h). In vitro assays demonstrated reduced viability in breast cancer (MCF-7, T47D, 4T1) and endothelial (C166) cells, enhanced synergistically by DOX (Av+DOX). Gene expression analysis revealed cell-specific modulation: Av+DOX upregulated and in T47D but suppressed both in 4T1/C166, suggesting context-dependent mechanisms. : These findings underscore avocado exosomes as promising nanovehicles for drug delivery, combining biocompatibility, metabolic functionality, and tunable cytotoxicity. Their plant-derived origin offers a scalable, low-cost alternative to mammalian exosomes, with potential applications in oncology and targeted therapy. Further optimization of loading efficiency and in vivo validation are warranted to advance translational prospects.
外泌体因其在药物递送方面的潜力最近受到了广泛关注。特别是植物来源的外泌体，由于其独特的特性，包括免疫原性、生物相容性、安全性、无细胞性质和纳米级结构，可能作为直接的抗癌剂。本研究对鳄梨来源的外泌体进行了表征，探索其抗癌特性、蛋白质组学特征和治疗潜力。分离出的外泌体直径在未负载时为99.58±5.09nm，负载阿霉素（DOX）时为151.2±6.36nm，ζ电位分别为-17mV和-28mV。蛋白质组学分析鉴定出47种蛋白质，包括保守的外泌体标志物（甘油醛-3-磷酸脱氢酶、微管蛋白）和应激反应蛋白（防御素、内切几丁质酶）。功能富集分析显示其在光合作用、糖酵解、ATP合成和跨膜运输中发挥作用，蛋白质-蛋白质相互作用网络突出了能量代谢和细胞运输。DOX包封效率为18%，具有持续释放特性（24小时时释放44.4%）。体外试验表明，其可降低乳腺癌（MCF-7、T47D、4T1）和内皮细胞（C166）的活力，DOX（Av+DOX）可增强这种作用。基因表达分析揭示了细胞特异性调节：Av+DOX在T47D中上调了和，但在4T1/C166中均下调，表明存在背景依赖性机制。这些发现强调了鳄梨外泌体作为有前景的药物递送纳米载体的潜力，其兼具生物相容性、代谢功能和可调节的细胞毒性。其植物来源为哺乳动物外泌体提供了一种可扩展、低成本的替代方案，在肿瘤学和靶向治疗中具有潜在应用。有必要进一步优化负载效率并进行体内验证，以推进转化前景。
