Department of Immunology, Nankai University School of Medicine, Tianjin, 300071, China.
J Biomed Nanotechnol. 2012 Oct;8(5):742-50. doi: 10.1166/jbn.2012.1442.
The inadequate treatment efficacy, suboptimal cancer detection and disease monitoring in anticancer therapies have led to the quest for clinically relevant, innovative multifaceted solutions such as development of targeted and traceable approaches. Molecular imaging technologies with the versatility of liposomal nanoparticles platform offer tangible options to better guide treatment delivery and monitor outcome. In this study, we introduced noninvasive, quantitative and functional imaging techniques with reporter gene methods to probe breast cancer processes with liposomal nanoparticles by bioluminescence imaging (BLI). A breast cancer model was applied for therapy by injecting 5.0 x 10(5) 4T1 cells carrying a reporter system encoding a double fusion reporter gene consisting of firefly luciferase (Fluc) and green fluorescent protein (GFP) into BALB/c mice. Liposomal nanoparticles loaded with a triple fusion gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk) and renilla luciferase (Rluc) and red fluorescent protein (RFP) were applied by in situ injection for monitoring and evaluating gene therapy. The BALB/c mice were subsequently treated with ganciclovir (GCV) and the growth status of tumor was monitored by bioluminescence imaging of Fluc and the treatment delivery of liposomal nanoparticle was efficiently tracked by Rluc imaging. In fact, TF plasmids were shown to be useful for monitoring and evaluating targeting efficacy and gene therapy by non-invasive molecular imaging. In conclusion, the combination of noninvasive imaging techniques and liposomal nanoparticle can provide a practical and clinically useful way for gene delivery and monitoring the level of gene expression over time and treatment response in patients undergoing gene therapy.
在癌症治疗中，疗效不足、癌症检测和疾病监测不理想，促使人们寻求临床相关的创新多方面解决方案，如开发靶向和可追踪的方法。具有多功能脂质体纳米颗粒平台的分子成像技术为更好地指导治疗提供了切实可行的选择，并监测治疗效果。在这项研究中，我们采用了无创、定量和功能成像技术以及报告基因方法，通过生物发光成像（BLI）研究脂质体纳米颗粒对乳腺癌的作用。通过将携带编码由萤火虫荧光素酶（Fluc）和绿色荧光蛋白（GFP）组成的双融合报告基因的 5.0 x 10(5) 4T1 细胞注射到 BALB/c 小鼠中，建立了乳腺癌模型，对其进行治疗。通过原位注射，脂质体纳米颗粒负载了包含单纯疱疹病毒截短胸苷激酶（HSV-ttk）和海肾荧光素酶（Rluc）和红色荧光蛋白（RFP）的三重融合基因，用于监测和评估基因治疗。随后，用更昔洛韦（GCV）治疗 BALB/c 小鼠，通过 Fluc 的生物发光成像监测肿瘤的生长状态，并通过 Rluc 成像有效追踪脂质体纳米颗粒的治疗传递。事实上，TF 质粒可用于通过非侵入性分子成像监测和评估靶向治疗效果和基因治疗。总之，非侵入性成像技术与脂质体纳米颗粒相结合，为基因传递提供了一种实用且在临床上有用的方法，并可随时间监测基因表达水平和基因治疗患者的治疗反应。
