Assessment of Therapeutic Efficacy of Liposomal Nanoparticles Mediated Gene Delivery by Molecular Imaging for Cancer Therapy

Assessment of Therapeutic Efficacy of Liposomal Nanoparticles Mediated Gene Delivery by Molecular Imaging for Cancer Therapy
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通过分子成像评估脂质体纳米粒子介导的基因传递对癌症治疗的疗效。

DOI:
10.1166/jbn.2012.1442
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发表时间:
2012-10-01
影响因子:
2.9
通讯作者:
Li, Zongjin
Li, Zongjin
中科院分区:
工程技术3区
文献类型:
--
作者:
Zhou, Manqian;Wang, Lina;Li, Zongjin

文献摘要

被引文献

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抗癌疗法中的治疗效果不足、癌症检测和疾病监测欠佳,导致人们寻求临床相关的创新多方面解决方案,例如开发有针对性和可追溯的方法。分子成像技术与脂质体纳米粒子平台的多功能性提供了切实的选择,以更好地指导治疗实施和监测结果。在这项研究中,我们引入了非侵入性、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)利用脂质体纳米颗粒探测乳腺癌过程。通过将携带报告系统的5.0×10(5)4T1细胞注射到BALB/c小鼠中来治疗乳腺癌模型,该细胞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。通过原位注射应用负载有包含单纯疱疹病毒截短胸苷激酶(HSV-ttk)、海肾荧光素酶(Rluc)和红色荧光蛋白(RFP)的三重融合基因的脂质体纳米颗粒来监测和评估基因治疗。随后用更昔洛韦(GCV)治疗 BALB/c 小鼠,并通过 Fluc 生物发光成像监测肿瘤的生长状态,并通过 Rluc 成像有效跟踪脂质体纳米颗粒的治疗递送。事实上,TF 质粒被证明可用于通过非侵入性分子成像监测和评估靶向功效和基因治疗。总之,无创成像技术和脂质体纳米颗粒的结合可以为基因递送和监测基因表达水平随时间的变化以及接受基因治疗的患者的治疗反应提供一种实用且临床有用的方法。
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.