Department of Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China; Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510640, China.
Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Int J Biol Macromol. 2020 Apr 1;148:483-492. doi: 10.1016/j.ijbiomac.2020.01.071. Epub 2020 Jan 8.
Redox-responsive theranostic nanoparticles based on poly-(N-ε-carbobenzyloxy-l-lysine) (PZLL) grafted hyaluronan (HA) (HA-g-SS-PZLL) copolymers were constructed for hepatocellular carcinoma diagnosis and therapy. These hyaluronan derivatives formed nanoparticles via a self-assembly process in aqueous solution at low concentration. Theranostic nanoparticles were obtained after loading hydrophobic doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) into the core of the nanoparticles via a dialysis method. Theranostic nanoparticles exhibited redox triggered DOX release behavior, and faster DOX released from theranostic nanoparticles was detected under a reducing environment compared with slow DOX release under a normal physiological environment. Confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining against HepG2 cells demonstrated that HA-g-SS-PZLL theranostic nanoparticles were capable of delivering DOX and SPIO into the cells. The analysis of the anticancer effect revealed that the HA-g-SS-PZLL theranostic nanoparticles shown higher cytotoxicity against HepG2 cells than DOX-loaded HA-g-PZLL nanoparticles. In vitro T magnetic resonance imaging (MRI) results exhibited that theranostic nanoparticles showed a good contrast enhancement effect, and the r relaxivity value was approximately 231 Fe mM s. Finally, the theranostic nanoparticles acted as nanoprobes for HepG2 tumor-bearing BALB/c mice for in vivo MRI. Therefore, HA-g-SS-PZLL copolymers have great potential as theranostic nanoparticles for tumor-targeted diagnosis and treatment.
基于聚（N-ε-羧基苄氧羰基-L-赖氨酸）（PZLL）接枝透明质酸（HA）（HA-g-SS-PZLL）共聚物的氧化还原响应治疗诊断纳米粒子被构建用于肝细胞癌的诊断和治疗。这些透明质酸衍生物在低浓度的水溶液中通过自组装过程形成纳米粒子。通过透析法将疏水性阿霉素（DOX）和超顺磁性氧化铁（SPIO）装载到纳米粒子的核心中，得到治疗诊断纳米粒子。治疗诊断纳米粒子表现出氧化还原触发的 DOX 释放行为，与在正常生理环境下缓慢释放 DOX 相比，在还原环境下检测到更快的治疗诊断纳米粒子中的 DOX 释放。共聚焦激光扫描显微镜（CLSM）、流式细胞术和普鲁士蓝染色对 HepG2 细胞的检测表明，HA-g-SS-PZLL 治疗诊断纳米粒子能够将 DOX 和 SPIO 递送到细胞中。抗癌效果分析表明，HA-g-SS-PZLL 治疗诊断纳米粒子对 HepG2 细胞的细胞毒性高于负载 DOX 的 HA-g-PZLL 纳米粒子。体外 T 磁共振成像（MRI）结果表明，治疗诊断纳米粒子表现出良好的对比增强效果，r 弛豫率值约为 231 Fe mM s。最后，治疗诊断纳米粒子作为纳米探针用于荷 HepG2 肿瘤的 BALB/c 小鼠的体内 MRI。因此，HA-g-SS-PZLL 共聚物具有作为肿瘤靶向诊断和治疗的治疗诊断纳米粒子的巨大潜力。
