Alhourani Abdelnour, Førde Jan-Lukas, Nasrollahzadeh Mojdeh, Eichacker Lutz Andreas, Herfindal Lars, Hagland Hanne Røland
Department of Chemistry, Biosciences and Environmental Engineering, University of Stavanger Stavanger Norway
Centre for Pharmacy, Department of Clinical Science, University of Bergen Bergen Norway.
Nanoscale Adv. 2022 Feb 9;4(6):1668-1680. doi: 10.1039/d1na00778e. eCollection 2022 Mar 15.
Graphene is an attractive choice for the development of an effective drug carrier in cancer treatment due to its high adsorption area and pH-responsive drug affinity. In combination with the highly potent metabolic drug phenformin, increased doses could be efficiently delivered to cancer cells. This study compares the use of graphene oxide (GO) and polyethylene glycol stabilized (PEGylated) pristine graphene nanosheets (PGNSs) for drug delivery applications with phenformin. The cytotoxicity and mitotoxicity of the graphene-based systems were assessed in human cells and zebrafish larvae. Targeted drug release from GO and PGNSs was evaluated at different pH levels known to arise in proliferating tumor microenvironments. PGNSs were less cytotoxic and mitotoxic than GO, and showed an increased release of phenformin at lower pH in cells, compared to GO. In addition, the systemic phenformin effect was mitigated in zebrafish larvae when bound to GO and PGNSs compared to free phenformin, as measured by flavin metabolic lifetime imaging. These results pave the way for improved phenformin-based cancer therapy using graphene nano-sheets, where PGNSs were superior to GO.
由于石墨烯具有高吸附面积和pH响应性药物亲和力，因此它是开发用于癌症治疗的有效药物载体的理想选择。与高效代谢药物二甲双胍联合使用时，可将增加的剂量有效地递送至癌细胞。本研究比较了氧化石墨烯（GO）和聚乙二醇稳定化（聚乙二醇化）的原始石墨烯纳米片（PGNSs）与二甲双胍在药物递送应用中的使用情况。在人类细胞和斑马鱼幼虫中评估了基于石墨烯的系统的细胞毒性和线粒体毒性。在已知在增殖性肿瘤微环境中出现的不同pH水平下评估了从GO和PGNSs的靶向药物释放。与GO相比，PGNSs的细胞毒性和线粒体毒性较小，并且在细胞中较低pH值下二甲双胍的释放量增加。此外，通过黄素代谢寿命成像测量，与游离二甲双胍相比，当与GO和PGNSs结合时，斑马鱼幼虫体内的全身二甲双胍效应得到缓解。这些结果为使用石墨烯纳米片改进基于二甲双胍的癌症治疗铺平了道路，其中PGNSs优于GO。
