利用多功能可生物降解金属有机框架 (bio-MOF) 中的姜黄素进行靶向结直肠癌治疗诊断。
Harnessing curcumin in a multifunctional biodegradable metal-organic framework (bio-MOF) for targeted colorectal cancer theranostics.
发表日期:2024 Sep 20
作者:
Maryam Babaei, Amir Abrishami, Sonia Iranpour, Amir Sh Saljooghi, Maryam M Matin
来源:
Drug Delivery and Translational Research
摘要:
尽管结直肠癌 (CRC) 的治疗取得了显着进步,但高效诊断和靶向治疗的问题仍然严峻。为了应对这些挑战并改善治疗结果,同时降低成本和副作用,需要更有效的治疗诊断系统,将诊断技术与治疗方式相结合。这项研究介绍了一种利用铁作为金属成分、姜黄素作为药物成分合成多孔生物 MOF(可生物降解金属有机框架)的开创性方法。随后,开发的药物递送系统配备了抗癌药物阿霉素(DOX),涂有生物相容性聚乙二醇(PEG),并靶向CRC特异性适体(EpCAM)。理化表征证实了生物 MOF 的成功合成,证明了 DOX 的高封装效率和 pH 依赖性释放。抗癌活性、细胞摄取和细胞死亡机制的体外研究表明,在 EpCAM HT-29 细胞呈阳性的情况下,Apt-PEG-MOF@DOX 增强了内化,导致大量细胞凋亡。然后在携带 HT-29 肿瘤的免疫功能低下的 C57BL/6 小鼠中进行纳米颗粒的体内研究。这些研究表明,靶向平台可以诱导有效的肿瘤消退,同时降低全身毒性。靶向生物 MOF 还表现出可用于监测肿瘤的 MRI 成像特性。值得注意的是,通过追求绿色合成方法,引入的生物MOF的生物相容性得到了增强,该方法不使用有毒溶剂和强酸。总体而言,这种多模式系统作为肿瘤显像剂和适合 CRC 治疗诊断的治疗递送平台具有多种作用。© 2024。控释协会。
Despite significant advancements in managing colorectal cancer (CRC), the issues of efficient diagnosis and targeted therapy remain demanding. To address these challenges and improve treatment outcomes while reducing the cost and side effects, there is a need for more effective theranostic systems that combine diagnostic techniques with therapeutic modalities. This study introduces a pioneering approach for the synthesis of a porous bio-MOF (biodegradable metal-organic framework) using iron as the metal component and curcumin as the pharmaceutical ingredient. Subsequently, the developed drug delivery system was equipped with the anticancer drug doxorubicin (DOX), coated with biocompatible polyethylene glycol (PEG), and targeted with a CRC-specific aptamer (EpCAM). The physicochemical characterization confirmed the successful synthesis of the bio-MOF, demonstrating high encapsulation efficiency and pH-dependent release of DOX. In vitro studies for anticancer activity, cellular uptake, and mechanism of cell death demonstrated that in the case of positive EpCAM HT-29 cells, Apt-PEG-MOF@DOX had enhanced internalization that resulted in massive apoptosis. In vivo studies of the nanoparticles were then conducted in immunocompromised C57BL/6 mice bearing HT-29 tumors. These studies showed that the targeted platform could induce efficient tumor regression with reduced systemic toxicity. The targeted bio-MOF also exhibited MRI imaging properties useful for monitoring tumors. Significantly, the biocompatibility of the introduced bio-MOF was enhanced by pursuing the green synthesis method, which does not engage toxic solvents and strong acids. Overall, this multimodal system acts diversely as a tumor imaging agent and a therapeutic delivery platform suitable for CRC theranostics.© 2024. Controlled Release Society.