Nabipour Hafezeh, Aliakbari Farhang, Volkening Kathryn, Strong Michael J, Rohani Sohrab
Department of Chemical and Biochemical Engineering, University of Western Ontario, London, ON N6A 5B9, Canada.
Translational Neuroscience Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada; Department of Bioprocess Engineering, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Int J Biol Macromol. 2025 Apr;301:140027. doi: 10.1016/j.ijbiomac.2025.140027. Epub 2025 Jan 20.
Metal-organic frameworks (MOFs) have shown great promise as pH-responsive drug delivery systems, with considerable potential for targeted cancer therapy. In this study, we synthesized a novel curcumin-loaded MOF, named UWO-2 (CUR@UWO-2), and developed its biocomposite form, CS-κ-Cr/CUR@UWO-2, by coating it with chitosan (CS) and κ-carrageenan (κ-Cr). Structural analysis through powder X-ray diffraction (PXRD) confirmed the successful synthesis of UWO-2 and the incorporation of CUR within the MOF structure. X-ray photoelectron spectroscopy (XPS) analysis revealed two distinct peaks at approximately 1021.15 eV and 1044.23 eV, corresponding to the Zn 2p₃/₂ and Zn 2p₁/₂ states, respectively. These peaks confirm the presence of the expected Zn oxidation state in UWO-2, further validating its successful synthesis. Brunauer-Emmett-Teller (BET) analysis demonstrated a significant decrease in surface area (367.4 m/g) and pore volume (0.296 cm/g), validating the entrapment of CUR within the UWO-2 MOF structure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed that UWO-2 particles are spherical with a smooth surface, while CUR@UWO-2 exhibited a larger particle size, indicating successful curcumin loading. Thermogravimetric analysis (TGA) indicated enhanced thermal stability due to CUR loading, while swelling experiments revealed increased water absorption at neutral pH, supporting effective drug release under physiological conditions. Biodegradation studies showed sustained degradation of CUR@UWO-2 in the presence of lysozyme, confirming its suitability for in-vivo applications. The drug delivery system achieved 21.9 % drug loading and 75.1 % encapsulation efficiency. Drug release experiments indicated accelerated release under acidic conditions, with the Korsmeyer-Peppas model identifying Fickian diffusion as the primary release mechanism. Cytotoxicity assessments showed increased cell death with CUR@UWO-2, enhanced by the synergistic effect of UWO-2, while the CS-κ-Cr coating enabled controlled, prolonged curcumin release. Confocal microscopy confirmed cellular uptake of CUR, underscoring the potential of the biocomposite for tumor-targeted chemotherapy applications in cancer treatment. This study highlights the potential of CUR@UWO-2, especially in its biocomposite form, for tumor-targeted drug delivery applications.
金属有机框架材料（MOFs）作为pH响应型药物递送系统已展现出巨大潜力，在靶向癌症治疗方面具有相当大的潜力。在本研究中，我们合成了一种新型的负载姜黄素的MOF，命名为UWO-2（CUR@UWO-2），并通过用壳聚糖（CS）和κ-卡拉胶（κ-Cr）包覆开发了其生物复合形式CS-κ-Cr/CUR@UWO-2。通过粉末X射线衍射（PXRD）进行的结构分析证实了UWO-2的成功合成以及姜黄素在MOF结构中的掺入。X射线光电子能谱（XPS）分析在约1021.15 eV和1044.23 eV处显示出两个不同的峰，分别对应于Zn 2p₃/₂和Zn 2p₁/₂态。这些峰证实了UWO-2中预期的Zn氧化态的存在，进一步验证了其成功合成。布鲁诺尔-埃米特-泰勒（BET）分析表明表面积（367.4 m/g）和孔体积（0.296 cm/g）显著降低，证实了姜黄素被包封在UWO-2 MOF结构中。扫描电子显微镜（SEM）和透射电子显微镜（TEM）图像显示UWO-2颗粒呈球形且表面光滑，而CUR@UWO-2的粒径更大，表明姜黄素成功负载。热重分析（TGA）表明由于负载姜黄素热稳定性增强，而溶胀实验显示在中性pH下吸水率增加，支持在生理条件下有效释放药物。生物降解研究表明在溶菌酶存在下CUR@UWO-2持续降解，证实了其适用于体内应用。该药物递送系统实现了21.9%的载药量和75.1%的包封率。药物释放实验表明在酸性条件下加速释放，Korsmeyer-Peppas模型确定菲克扩散为主要释放机制。细胞毒性评估显示CUR@UWO-2导致细胞死亡增加，UWO-2的协同作用增强了这种效果，而CS-κ-Cr涂层能够实现姜黄素的可控、长效释放。共聚焦显微镜证实了姜黄素的细胞摄取，强调了该生物复合材料在癌症治疗中肿瘤靶向化疗应用的潜力。本研究突出了CUR@UWO-2，特别是其生物复合形式在肿瘤靶向药物递送应用中的潜力。
