State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China.
Medical Imaging Center, the First Affiliated Hospital, Jinan University, No. 613 West Huangpu Avenue, Tianhe District, Guangzhou 510630, China; Department of Radiology, Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 516000, China.
J Inorg Biochem. 2022 Oct;235:111940. doi: 10.1016/j.jinorgbio.2022.111940. Epub 2022 Jul 23.
Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of HO to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of HO, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (O). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.
尽管已经开发出许多用于肿瘤治疗的方法,但治疗过程中缺乏有效的成像指导仍然是一个亟待解决的问题。在本研究中,将(Gd)螯合在 CuS 纳米粒子上的磁共振对比剂和葡萄糖氧化酶(GOx)共负载到介孔硅纳米粒子(MSNs)中,形成 GOx-Gd-CuS@MSNs,其中 Gd 提供磁共振成像(MRI)用于治疗过程监测,而 GOx 可以催化 HO 的生成,以增强光动力治疗(PDT)。体外实验结果表明,在近红外(NIR)激光照射(2 W·cm,5 min)下,由于热量的积累,温度迅速升高约 30°C。同时,GOx-Gd-CuS@MSNs 上的 GOx 有效地消耗葡萄糖以产生大量的 HO,通过产生高毒性的羟基自由基(·OH)和单线态氧(O)来增强 PDT。光热和增强的光动力可以诱导肿瘤细胞凋亡和死亡。更重要的是,研究发现 GOx-Gd-CuS@MSNs 具有 MRI 性能,可以在治疗过程中提供成像指导,并且可以监测治疗过程中肿瘤组织中水分子的扩散和毛细血管网络的微循环灌注。这些结果表明,该纳米材料通过光热和光动力产生了显著的协同治疗效果,同时在成像中具有出色的空间分辨率和深组织穿透能力。