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A Laser-Activated Multifunctional Targeted Nanoagent for Imaging and Gene Therapy in a Mouse Xenograft Model with Retinoblastoma Y79 Cells
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2018-02-13 , DOI: 10.1016/j.actbio.2018.02.006
Mingxing Wu , Haibo Xiong , Hongmi Zou , Meng Li , Pan Li , Yu Zhou , Yan Xu , Jia Jian , Fengqiu Liu , Hongyun Zhao , Zhigang Wang , Xiyuan Zhou

Retinoblastoma (RB) is the most common intraocular malignancy of childhood that urgently needs early detection and effective therapy methods. The use of nanosized gene delivery systems is appealing because of their highly adjustable structure to carry both therapeutic and imaging agents. Herein, we report a folic acid (FA)-modified phase-changeable cationic nanoparticle encapsulating liquid perfluoropentane (PFP) and indocyanine green (ICG) (FA-CN-PFP-ICG, FCNPI) with good plasmid DNA (pDNA) carrying capacity, favorable biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, enhanced gene transfection efficiency and therapeutic effect. The liquid-gas phase transition of the FCNPI upon laser irradiation has provided splendid contrasts for US/PA dual-modality imaging in vitro as well as in vivo. More importantly, laser-mediated gene transfection with targeted cationic FCNPI nanoparticles demonstrated the best therapeutic effect compared with untargeted cationic nanoparticle (CN-PFP-ICG, CNPI) and neutral nanoparticle (NN-PFP-ICG, NNPI), both in vitro and in vivo. Such a multifunctional nanoagent is expected to combine dual-mode guided imaging with fewer side effects and proper therapeutic efficacy. These results establish an experimental foundation for the clinical detection of and therapy for RB.

Statement of significance

We successfully constructed a multifunctional targeted cationic nanoparticle (FCNPI) and meticulously compared the variations in the plasmid loading capacity and binding to Y79 cells with NNPI, CNPI, and FCNPI. FCNPI exhibited favorable plasmid loading capability, splendid ability for targeting and only it could provide optimal US and PA contrast to background during a considerable long time. The FCNPI/pDNA+Laser system also exhibited the best therapeutic effect in vivo; this finding proposes a potential strategy for the evaluation of an efficient gene delivery nanocarrier for gene targeting therapy of RB tumor. Our study showed that there are great advantages of targeting FCNPI to provide PA/US imaging and to enlighten laser-mediated gene transfection. FCNPI is a very helpful multifunctional agent with potential.



中文翻译:

激光激活多功能靶向纳米试剂的视网膜母细胞瘤Y79细胞的小鼠异种移植模型中的成像和基因治疗。

视网膜母细胞瘤(RB)是儿童期最常见的眼内恶性肿瘤,迫切需要早期发现和有效的治疗方法。纳米级基因递送系统的使用具有吸引力,因为它们具有高度可调节的结构,可同时携带治疗剂和成像剂。在本文中,我们报道了叶酸(FA)修饰的相变阳离子纳米颗粒,其包裹着液态全氟戊烷(PFP)和吲哚菁绿(ICG)(FA-CN-PFP-ICG,FCNPI),具有良好的质粒DNA(pDNA)携带能力,良好的生物相容性,出色的光声(PA)和超声(US)对比度,增强的基因转染效率和治疗效果。FCNPI在激光辐照下的液相-气相转变为US / PA体外和体内双峰成像提供了出色的对比。更重要的是,激光靶向介导的FCNPI纳米粒子的基因转染在体外和体内均表现出与非靶向阳离子纳米粒子(CN-PFP-ICG,CNPI)和中性纳米粒子(NN-PFP-ICG,NNPI)相比最佳的治疗效果。期望这种多功能纳米剂将双模式引导的成像与更少的副作用和适当的治疗功效相结合。这些结果为RB的临床检测和治疗奠定了实验基础。期望这种多功能纳米剂将双模式引导的成像与更少的副作用和适当的治疗功效相结合。这些结果为RB的临床检测和治疗奠定了实验基础。期望这种多功能纳米剂将双模式引导的成像与更少的副作用和适当的治疗功效相结合。这些结果为RB的临床检测和治疗奠定了实验基础。

重要声明

我们成功构建了多功能靶向阳离子纳米颗粒(FCNPI),并用NNPI,CNPI和FCNPI精心比较了质粒负载能力和与Y79细胞结合的变化。FCNPI表现出良好的质粒加载能力,出色的靶向能力,并且只有在相当长的时间内才能提供与背景最佳的US和PA对比。FCNPI / pDNA + Laser系统在体内也表现出最佳的治疗效果。该发现提出了用于评估RB肿瘤的基因靶向治疗的有效基因递送纳米载体的潜在策略。我们的研究表明,靶向FCNPI具有很大的优势,可提供PA / US成像并启发激光介导的基因转染。FCNPI是一种很有潜力的多功能助剂。

更新日期:2018-02-14
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