Abstract：
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 evaluatedin vivotherapeutic potential, and tumor tissues were examined using H&E staining andin vivoimaging. SHK-Exos demonstrated effective cell targeting and internalization in CRC cells.In vitro, SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, whilein vivostudies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Employing SHK-Exos effectively impedes CRC progressionin vitroandin vivo, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.
摘要：
背景：结直肠癌（CRC）是一种常见的恶性肿瘤，死亡率高，预后差。紫草素（SHK）已在各种癌症中表现出广泛的抗肿瘤活性，然而，其临床应用受到溶解度差的阻碍，有限的生物利用度，和高毒性。本研究旨在开发负载SHK的外泌体（SHK-Exos）并评估其在CRC进展中的功效。
材料与方法：外泌体采用超速离心法分离，并通过TEM表征,NTA,和西方印迹。通过PKH67标记后的共聚焦显微镜确认它们的细胞内化。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细胞凋亡。异种移植肿瘤模型评估体内治疗潜力，使用H&E染色和体内成像检查肿瘤组织。结果:SHK-Exos在CRC细胞中证明了有效的细胞靶向和内化。体外，SHK-Exos在抑制侵袭性细胞行为和促进细胞凋亡方面超越了游离SHK，而体内研究显示，在减少肿瘤生长方面具有显着的功效，具有出色的肿瘤靶向性和最小的毒性。＆＃xD;结论：使用SHK-Exos有效地阻止了CRC在体外和体内的进展，提供显著的治疗潜力。这项研究强调了使用自体外泌体作为药物载体的优势，增强疗效和减少毒性。
