Thapa Raj Kumar, Choi Ju Yeon, Poudel Bijay Kumar, Choi Han-Gon, Yong Chul Soon, Kim Jong Oh
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsanbuk-do, South Korea.
College of Pharmacy, Hanyang University, Ansan, South Korea.
Int J Nanomedicine. 2016 Jun 13;11:2799-813. doi: 10.2147/IJN.S105401. eCollection 2016.
Cancer is one of the leading causes of death worldwide. Although different chemotherapeutic agents have been developed to treat cancers, their use can be limited by low cellular uptake, drug resistance, and side effects. Hence, targeted drug delivery systems are continually being developed in order to improve the efficacy of chemotherapeutic agents. The main aim of this study was to prepare folic acid (FA)-conjugated polyvinyl pyrrolidone-functionalized graphene oxides (GO) (FA-GO) for targeted delivery of sorafenib (SF). GO were prepared using a modified Hummer's method and subsequently altered to prepare FA-GO and SF-loaded FA-GO (FA-GO/SF). Characterization of GO derivatives was done using ultraviolet/visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic force microscopy, zeta potential measurements, and determination of in vitro drug release. Hemolytic toxicity, in vitro cytotoxicity, cellular uptake, and apoptotic effects of FA-GO/SF were also investigated. The results revealed that GO was successfully synthesized and that further transformation to FA-GO improved the stability and SF drug-loading capacity. In addition, the enhanced SF release under acidic conditions suggested possible benefits for cancer treatment. Conjugation of FA within the FA-GO/SF delivery system enabled targeted delivery of SF to cancer cells expressing high levels of FA receptors, thus increasing the cellular uptake and apoptotic effects of SF. Furthermore, the photothermal effect achieved by exposure of GO to near-infrared irradiation enhanced the anticancer effects of FA-GO/SF. Taken together, FA-GO/SF is a potential carrier for targeted delivery of chemotherapeutic agents in cancer.
癌症是全球主要死因之一。尽管已开发出不同的化疗药物来治疗癌症，但它们的使用可能会受到细胞摄取率低、耐药性和副作用的限制。因此，为了提高化疗药物的疗效，靶向给药系统不断被开发出来。本研究的主要目的是制备叶酸（FA）共轭的聚乙烯吡咯烷酮功能化氧化石墨烯（GO）（FA-GO），用于索拉非尼（SF）的靶向递送。采用改良的Hummer法制备GO，随后将其改性以制备FA-GO和负载SF的FA-GO（FA-GO/SF）。使用紫外/可见光谱、傅里叶变换红外光谱、X射线衍射、原子力显微镜、zeta电位测量以及体外药物释放测定对GO衍生物进行表征。还研究了FA-GO/SF的溶血毒性、体外细胞毒性、细胞摄取和凋亡作用。结果表明，成功合成了GO，进一步转化为FA-GO提高了稳定性和SF载药能力。此外，在酸性条件下SF释放增强表明对癌症治疗可能有益。FA在FA-GO/SF递送系统中的共轭使得SF能够靶向递送至高表达FA受体的癌细胞，从而增加了SF的细胞摄取和凋亡作用。此外，GO暴露于近红外辐射所实现的光热效应增强了FA-GO/SF的抗癌作用。综上所述，FA-GO/SF是癌症化疗药物靶向递送的潜在载体。
