Gao Wenbin, Wei Shipan, Li Zhuo, Li Lei, Zhang Xuwu, Li Chunhui, Gao Dawei
State Key Laboratory of Metastable Materials Science and Technology, Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004, People's Republic of China.
Nanotechnology. 2020 Aug 28;31(35):355104. doi: 10.1088/1361-6528/ab92c8. Epub 2020 May 13.
Multifunctional nanoplatforms yield extremely high synergistic therapeutic effects on the basis of low biological toxicity. Based on the unique tumor microenvironment (TME), a liposomes (Lips)-based multifunctional antitumor drug delivery system known as GOD-PTL-Lips@MNPs was synthesized for chemotherapy, chemodynamic therapy (CDT), starvation therapy, and magnetic targeting synergistic therapy. Evidence has suggested that parthenolide (PTL) can induce apoptosis and consume excessive glutathione (GSH), thereby increasing the efficacy of chemodynamic therapy. On the other hand, glucose oxidase (GOD) can consume intratumoral glucose, lower pH and increase the level of HO in the tumor tissue. Integrated FeO magnetic nanoparticles (MNPs) containing Fe and Fe effectively catalyzes HO to a highly toxic hydroxyl radical (•OH) and provide magnetic targeting. During the course of in vitro and in vivo experiments, GOD-PTL-Lips@MNPs demonstrated remarkable synergistic antitumor efficacy. In particular, in mice receiving a 14 day treatment of GOD-PTL-Lips@MNPs, tumor growth was significantly inhibited, as compared with the control group. Moreover, toxicology study and histological examination demonstrated low biotoxicity of this novel therapeutic approach. In summary, our data suggests great antitumor potential for GOD-PTL-Lips@MNPs which could provide an alternative means of further improving the efficacy of anticancer therapies.
多功能纳米平台在低生物毒性的基础上产生极高的协同治疗效果。基于独特的肿瘤微环境（TME），合成了一种基于脂质体（Lips）的多功能抗肿瘤药物递送系统，即GOD-PTL-Lips@MNPs，用于化疗、化学动力学疗法（CDT）、饥饿疗法和磁靶向协同治疗。有证据表明，小白菊内酯（PTL）可诱导细胞凋亡并消耗过量的谷胱甘肽（GSH），从而提高化学动力学疗法的疗效。另一方面，葡萄糖氧化酶（GOD）可消耗肿瘤内的葡萄糖，降低pH值并提高肿瘤组织中HO的水平。含有Fe和Fe的集成FeO磁性纳米颗粒（MNPs）有效地将HO催化为高毒性的羟基自由基（•OH）并提供磁靶向。在体外和体内实验过程中，GOD-PTL-Lips@MNPs表现出显著的协同抗肿瘤疗效。特别是，在接受GOD-PTL-Lips@MNPs治疗14天的小鼠中，与对照组相比，肿瘤生长受到显著抑制。此外，毒理学研究和组织学检查表明这种新型治疗方法的生物毒性较低。总之，我们的数据表明GOD-PTL-Lips@MNPs具有巨大的抗肿瘤潜力，可为进一步提高抗癌治疗疗效提供替代手段。
