Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China; Department of Ophthalmology, Chongqing General Hospital, Chongqing 400010, PR China.
Acta Biomater. 2018 Apr 1;70:211-226. doi: 10.1016/j.actbio.2018.02.006. Epub 2018 Feb 13.
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.
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.
视网膜母细胞瘤（RB）是儿童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。纳米级基因传递系统因其高度可调的结构而具有吸引力，可携带治疗剂和成像剂。在此，我们报告了一种叶酸（FA）修饰的相变型阳离子纳米颗粒，该纳米颗粒包封液态全氟戊烷（PFP）和吲哚菁绿（ICG）（FA-CN-PFP-ICG，FCNPI），具有良好的质粒 DNA（pDNA）载量、良好的生物相容性、优异的光声（PA）和超声（US）对比、增强的基因转染效率和治疗效果。激光照射下 FCNPI 的液-气相转变为体外和体内 US/PA 双模态成像提供了极好的对比。更重要的是，与非靶向阳离子纳米颗粒（CN-PFP-ICG，CNPI）和中性纳米颗粒（NN-PFP-ICG，NNPI）相比，激光介导的靶向阳离子 FCNPI 纳米颗粒转染显示出最佳的治疗效果，无论是在体外还是体内。这种多功能纳米制剂有望将双模式引导成像与更少的副作用和适当的治疗效果相结合。这些结果为 RB 的临床检测和治疗奠定了实验基础。
我们成功构建了一种多功能靶向阳离子纳米颗粒（FCNPI），并详细比较了 NNPI、CNPI 和 FCNPI 的质粒载量和与 Y79 细胞结合的变化。FCNPI 表现出良好的质粒载量能力，出色的靶向能力，只有它才能在相当长的时间内提供最佳的 US 和 PA 对比背景。FCNPI/pDNA+激光系统在体内也显示出最佳的治疗效果；这一发现为评价 RB 肿瘤基因靶向治疗的高效基因传递纳米载体提供了一种潜在策略。我们的研究表明，靶向 FCNPI 提供 PA/US 成像和启发激光介导基因转染具有很大的优势。FCNPI 是一种非常有帮助的多功能制剂，具有潜力。
