Department of Radiology, Lishui Hospital of Zhejiang University, Lishui, China; Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Nanomedicine. 2018 Oct;14(7):2167-2178. doi: 10.1016/j.nano.2018.06.014. Epub 2018 Jul 12.
Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02 mM s) than commercial MR contrast agent Gd-DTPA (3.3765 mM s). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment.
有效的肝癌治疗和实时监测至关重要。本研究开发了一种多功能磷酸钙纳米粒子负载化疗药物阿霉素和磁共振成像造影剂二乙三胺五乙酸钆（A54-CaP/Gd-DTPA/DOX），通过 T1 加权磁共振成像实时实现肝癌的可视化靶向治疗。A54-CaP/Gd-DTPA/DOX 的纵向弛豫率（6.02 mM s）高于商业磁共振造影剂 Gd-DTPA（3.3765 mM s）。纳米粒子中 DOX 的释放表现出 pH 依赖性行为。细胞摄取结果表明，通过 A54 结合，A54-CaP/Gd-DTPA/DOX 进入 BEL-7402 细胞的内化速度比 HepG2 细胞快 1.9 倍。体内实验表明，与 CaP/Gd-DTPA/DOX 和游离 DOX 相比，A54-CaP/Gd-DTPA/DOX 在肿瘤组织中的分布更高，保留时间更长，并且具有更好的抗肿瘤疗效（95.38%的肿瘤抑制率）和更低的毒性。此外，纳米粒子中包裹的 Gd-DTPA 可提供 T1 加权磁共振成像，实时监测肿瘤治疗进展。
