Babaei Maryam, Abrishami Amir, Iranpour Sonia, Saljooghi Amir Sh, Matin Maryam M
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Drug Deliv Transl Res. 2025 May;15(5):1719-1738. doi: 10.1007/s13346-024-01707-6. Epub 2024 Sep 20.
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.
尽管在结直肠癌（CRC）的管理方面取得了重大进展，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，在降低成本和副作用的同时改善治疗效果，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。本研究引入了一种开创性的方法，以铁作为金属成分、姜黄素作为药物成分来合成多孔生物金属有机框架（bio-MOF，可生物降解的金属有机框架）。随后，所开发的药物递送系统装载了抗癌药物阿霉素（DOX），用生物相容性聚乙二醇（PEG）包被，并以CRC特异性适配体（EpCAM）作为靶向分子。物理化学表征证实了bio-MOF的成功合成，显示出高包封效率和DOX的pH依赖性释放。关于抗癌活性、细胞摄取和细胞死亡机制的体外研究表明，对于EpCAM阳性的HT-29细胞，Apt-PEG-MOF@DOX具有增强的内化作用，导致大量细胞凋亡。然后在携带HT-29肿瘤的免疫缺陷C57BL/6小鼠中进行了纳米颗粒的体内研究。这些研究表明，该靶向平台可诱导有效的肿瘤消退，同时降低全身毒性。靶向bio-MOF还表现出对监测肿瘤有用的MRI成像特性。值得注意的是，通过采用不使用有毒溶剂和强酸的绿色合成方法，提高了所引入bio-MOF的生物相容性。总体而言，这种多模态系统具有多种功能，可作为肿瘤成像剂和适用于CRC治疗诊断的治疗递送平台。
