Abstract:
Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.
摘要:
癌症仍然是全球死亡的主要原因之一,缺乏有效的治疗。常规疗法在肿瘤特异性和非特异性毒性方面的固有缺点促使我们寻找替代疗法来减轻这些限制。在这方面,我们开发了多功能双金属(FeCo)双MIL-88B-FCMOFs修饰的叶酸偶联壳聚糖(FC)作为药物递送系统(DDS)靶向递送5-氟尿嘧啶(5-FU)。双MIL-88B纳米载体通过各种技术进行了表征,包括粉末X射线衍射,扫描电子显微镜,能量色散X射线,热重分析,和傅里叶变换红外光谱。有趣的是,与未改性的5-FU@bi-MIL-88B相比,由于FC表面涂层赋予的门控效应现象,5-FU@bi-MIL-88B-FC显示出较慢的5-FU释放。观察到pH响应的药物释放,58%的加载的5-FU在模拟pH(5.2)的癌细胞中释放,而在生理pH下仅释放24.9%(5.4)。体外细胞毒性和细胞内化实验揭示了5-FU@bi-MIL-88B-FC作为针对叶酸受体(FR)阳性SW480癌细胞的高效靶向DDS的优越性。此外,由于结构中存在Fe和Co,bi-MIL-88B表现出用于化学动力学治疗的过氧化物酶样活性。根据结果,5-FU@bi-MIL-88B-FC可以通过持续的药物释放和选择性靶向作为智能DDS的有希望的候选物。