Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Nanotechnology. 2024 Jul 23;35(41). doi: 10.1088/1361-6528/ad61f2.
Colorectal cancer (CRC) is a prevalent malignancy with high mortality rates and poor prognosis. Shikonin (SHK) has demonstrated extensive anti-tumor activity across various cancers, yet its clinical application is hindered by poor solubility, limited bioavailability, and high toxicity. This study aims to develop SHK-loaded exosomes (SHK-Exos) and assess their efficacy in CRC progression. Exosomes were isolated using ultracentrifugation and characterized via TEM, NTA, and western blotting. Their cellular internalization was confirmed through confocal microscopy post PKH67 labeling. Effects on cell behaviors were assessed using CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed via flow cytometry. A xenograft tumor model evaluatedtherapeutic potential, and tumor tissues were examined using H&E staining andimaging. SHK-Exos demonstrated effective cell targeting and internalization in CRC cells., SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, whilestudies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Employing SHK-Exos effectively impedes CRC progressionand, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.
结直肠癌(CRC)是一种高发恶性肿瘤,死亡率和预后较差。紫草素(SHK)在多种癌症中表现出广泛的抗肿瘤活性,但由于溶解度差、生物利用度有限和毒性高,其临床应用受到限制。本研究旨在开发负载紫草素的外泌体(SHK-Exos),并评估其在 CRC 进展中的疗效。使用超速离心法分离外泌体,并通过 TEM、NTA 和 Western blot 进行表征。通过 PKH67 标记后的共聚焦显微镜确认其细胞内化。使用 CCK-8 和 Transwell 测定评估对细胞行为的影响。通过流式细胞术分析细胞周期和凋亡。使用异种移植肿瘤模型评估治疗潜力,并使用 H&E 染色和成像检查肿瘤组织。SHK-Exos 显示出对 CRC 细胞的有效靶向和内化作用。与游离 SHK 相比,SHK-Exos 更能抑制侵袭性细胞行为并促进凋亡,同时在减少肿瘤生长方面表现出显著的疗效,具有良好的肿瘤靶向性和最小的毒性。使用 SHK-Exos 可有效抑制 CRC 进展,具有显著的治疗潜力。这项研究强调了使用自体外泌体作为药物载体的优势,可提高疗效并降低毒性。