Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
Int J Biol Macromol. 2024 Aug;275(Pt 2):133625. doi: 10.1016/j.ijbiomac.2024.133625. Epub 2024 Jul 31.
Exosomes (Exos), natural nanovesicles released by various cell types, show potential as an effective drug delivery platform due to their intrinsic role as transporters of biomolecules between different cells. However, Exos functionalization with targeting ligands is a critical step to enhance their targeting capability, which could be challenging. In this study, Exos were modified to specifically bind to CD44-positive cells by anchoring chondroitin sulfate (CS) to their surface. Exo modification was facilitated with CS conjugation with alpha-tocopherol succinate (TOS) as an anchorage. The modified Exos were utilized for delivering curcumin (Cur) to pancreatic cancer (PC) cells. In vitro Cur release studies revealed that Exos play a crucial role in maintaining Cur within themselves, demonstrating their potential as effective carriers for drug delivery to targeted locations. Notably, Cur loaded into the modified Exos exhibited enhanced cytotoxicity compared to unmodified Exo-Cur. Meanwhile, Exo-Cur-TOS-CS induced apoptosis more effectively in AsPC-1 cells than unmodified Exos (70.2 % versus 56.9 %). It is worth mentioning that with CD44-mediated cancer-specific targeting, Exo-CS enabled increased intracellular accumulation in AsPC-1 cells, showing promise as a targeted platform for cancer therapy. These results confirm that Exo modification has a positive impact on enhancing the therapeutic efficacy and cytotoxicity of drugs.
外泌体（Exos）是各种细胞释放的天然纳米囊泡，由于它们在不同细胞之间作为生物分子转运体的内在作用，具有作为有效药物递送平台的潜力。然而，通过靶向配体对外泌体进行功能化是增强其靶向能力的关键步骤，这可能具有挑战性。在这项研究中，通过将软骨素硫酸盐（CS）锚定到其表面，使外泌体特异性结合 CD44 阳性细胞。通过将 CS 与生育酚琥珀酸酯（TOS）缀合来促进外泌体的修饰，作为锚定物。修饰后的外泌体用于将姜黄素（Cur）递送至胰腺癌细胞（PC）。体外 Cur 释放研究表明，外泌体在维持自身内的 Cur 方面发挥着至关重要的作用，这表明它们具有作为药物递送至靶向部位的有效载体的潜力。值得注意的是，与未修饰的 Exo-Cur 相比，负载到修饰的外泌体中的 Cur 表现出增强的细胞毒性。同时，与未修饰的外泌体相比，Exo-Cur-TOS-CS 在 AsPC-1 细胞中更有效地诱导细胞凋亡（70.2%对 56.9%）。值得一提的是，通过 CD44 介导的癌症特异性靶向，Exo-CS 能够增加 AsPC-1 细胞内的细胞内积累，显示出作为癌症治疗的靶向平台的潜力。这些结果证实了外泌体修饰对增强药物的治疗效果和细胞毒性具有积极影响。
