Jiang Ling, Chi Jiaying, Wang Jiahui, Fang Shaobin, Peng Tingting, Quan Guilan, Liu Daojun, Huang Zhongjie, Lu Chao
Department of Pharmacy, Shantou University Medical College, Shantou 515041, China.
College of Pharmacy, Jinan University, Guangzhou 511436, China.
Pharmaceutics. 2023 Aug 25;15(9):2205. doi: 10.3390/pharmaceutics15092205.
Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T relaxivity value 5.5 times higher than that of Resovist. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.
超顺磁性氧化铁（SPIO）纳米晶体作为一种诊疗纳米粒子已被广泛研究，以提高横向（T）弛豫率并增强磁共振成像（MRI）中的对比度。为了延长血液循环时间并提高MRI造影剂的诊断灵敏度，我们开发了一种两亲性共聚物PCPZL，以有效包封SPIO纳米晶体。PCPZL是通过将基于聚乙二醇（PEG）的同双功能连接体与疏水性星状聚（ε-苄氧羰基-L-赖氨酸）链段交联而合成的。因此，它可以自组装成壳交联胶束，在血液循环中具有增强的胶体稳定性。值得注意的是，PCPZL可以以66.0±0.9%的高负载量有效负载SPIO纳米晶体，形成直径约为100 nm、簇密度高且T弛豫率值比Resovist高5.5倍的SPIO纳米簇。体内MRI测量突出了负载SPIO的PCPZL胶束在健康小鼠和原位肝细胞癌肿瘤模型裸鼠肝脏中的快速积累和造影效果。此外，磁性胶束显著增强了肿瘤与正常肝组织之间的相对MRI信号差异。总体而言，我们的研究结果表明，PCPZL显著提高了SPIO纳米晶体的稳定性和磁性，使负载SPIO的PCPZL胶束成为用于诊断肝脏疾病和癌症的有前景的MRI造影剂。
