Liu Yongjun, Li Junsheng, Liu Fengxi, Feng Lixia, Yu Dexin, Zhang Na
J Biomed Nanotechnol. 2015 Apr;11(4):613-22. doi: 10.1166/jbn.2015.1945.
Theranostics, which combine molecular imaging (diagnostics) and drug delivery (therapeutics) in a single platform, have recently shown great potential in cancer therapy. In this article, a polymeric micelle was designed and prepared for simultaneous magnetic resonance imaging (MRI) and treatment of hepatocellular carcinoma (HCC). Theranostic micelles were assembled using Poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and PLA-PEG-PLL-Biotin. The HCC therapeutic paclitaxel (PTX) was encapsulated in the cores and Gd ions for imaging were chelated to the DTPA moieties. Biotinylated alpha-fetoprotein (AFP) antibodies were linked to the micelle surface by a biotin-avidin reaction to form targeted Gd/PTX-loaded micelles (TGPM). TGPM were of spherical or ellipsoidal shape with uniform particle size distribution (147.50 ± 4.71 nm), positive zeta potential (24.45 ± 1.04 mV), and high encapsulation efficiency (88.76 ± 1.64%) and drug loading (1.59 ± 0.06%). The cytotoxicity of TGPM in HepG2 cells was superior to that of Taxol or Gd/PTX-loaded micelles (GPM). In MRI tests in vitro, the T1 relaxivity of TGPM was 21.589 mM(-1) s(-1), 4.4 times higher than Magnevist (r1 = 4.8 mM(-1) s(-1)). In H22 tumor-bearing mice, TGPM significantly increased tumor imaging intensity (more than 3 times) and prolonged imaging time (from 1 to 6 h) compared to Magnevist. In vivo, TGPM exhibited higher anti-tumor efficiency than Taxol and GPM. These results indicate that TGPM has great potential in HCC theranostics.
诊疗一体化技术将分子成像（诊断）和药物递送（治疗）整合于单一平台，近年来在癌症治疗中展现出巨大潜力。在本文中，设计并制备了一种用于同时进行磁共振成像（MRI）和治疗肝细胞癌（HCC）的聚合物胶束。使用聚乳酸-聚乙二醇-聚L-赖氨酸-二乙三胺五乙酸（PLA-PEG-PLL-DTPA）和PLA-PEG-PLL-生物素组装诊疗一体化胶束。将HCC治疗药物紫杉醇（PTX）包裹于核内，将用于成像的钆离子螯合至DTPA部分。通过生物素-抗生物素蛋白反应将生物素化的甲胎蛋白（AFP）抗体连接至胶束表面，形成靶向载钆/紫杉醇胶束（TGPM）。TGPM呈球形或椭圆形，粒径分布均匀（147.50±4.71 nm），ζ电位为正（24.45±1.04 mV），且具有较高的包封率（88.76±1.64%）和载药量（1.59±0.06%）。TGPM对HepG2细胞的细胞毒性优于紫杉醇或载钆/紫杉醇胶束（GPM）。在体外MRI测试中，TGPM的纵向弛豫率为21.589 mM⁻¹ s⁻¹，比马根维显（r1 = 4.8 mM⁻¹ s⁻¹）高4.4倍。在荷H22肿瘤小鼠中，与马根维显相比，TGPM显著提高了肿瘤成像强度（超过3倍）并延长了成像时间（从1小时延长至6小时）。在体内，TGPM表现出比紫杉醇和GPM更高的抗肿瘤效率。这些结果表明TGPM在HCC诊疗一体化方面具有巨大潜力。
