National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao, China.
J Mater Chem B. 2019 Apr 7;7(13):2190-2200. doi: 10.1039/c8tb03320j. Epub 2019 Feb 27.
Cancer cells possess some inherent characteristics, such as glucose-dependence and intolerance to heat and exogenous reactive oxygen species (ROS). In this study, a strategy has been developed to target these vulnerable weaknesses of cancer cells using glucose oxidase (GOx) and polydopamine (PDA) functionalized iron oxide nanoparticles (FeO@PDA/GOx NPs). PDA is first deposited on the surfaces of iron oxide NPs through self-polymerization, and then GOx is covalently linked with PDA upon mixing the enzyme and FeO@PDA under alkaline conditions. In this system, the PDA layer along with iron oxide NPs serves as a photothermal transfer material converting near infrared (NIR) radiation into heat. The covalently linked GOx can competitively consume glucose and spontaneously generate ROS HO that can be further converted by the iron oxide NPs into more toxic ˙OH, inducing apoptosis of cancer cells. The selective toxicity of FeO@PDA/GOx NPs on cancer cells is demonstrated both in vitro and in vivo. In particular, a single injection rather than multiple doses results in significant suppression of tumors, and does not induce apparent histological lesions in the 4T1 tumor-bearing Balb/c mice. The versatility of the functionalization strategy reported in this study will contribute to developing efficient therapies for selective cancer treatment.
癌细胞具有一些固有特性,如葡萄糖依赖性、不耐热和对外源活性氧物种 (ROS) 的不耐受性。在这项研究中,我们开发了一种使用葡萄糖氧化酶 (GOx) 和聚多巴胺 (PDA) 功能化氧化铁纳米颗粒 (FeO@PDA/GOx NPs) 靶向这些癌细胞脆弱弱点的策略。首先通过自聚合在氧化铁 NPs 表面沉积 PDA,然后在混合酶和 FeO@PDA 时在碱性条件下使 GOx 与 PDA 发生共价连接。在该体系中,PDA 层和氧化铁 NPs 作为光热传递材料,将近红外 (NIR) 辐射转化为热量。共价连接的 GOx 可以竞争性地消耗葡萄糖并自发产生 ROS HO,HO 可以被氧化铁 NPs 进一步转化为更有毒的˙OH,诱导癌细胞凋亡。FeO@PDA/GOx NPs 对癌细胞的选择性毒性在体外和体内都得到了证明。特别是,单次注射而不是多次注射就能显著抑制肿瘤,并且不会在荷 4T1 肿瘤的 Balb/c 小鼠中引起明显的组织学损伤。本研究中报道的功能化策略的多功能性将有助于开发用于选择性癌症治疗的有效疗法。