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A laser-activated multifunctional targeted nanoagent for imaging and gene therapy in a mouse xenograft model with retinoblastoma Y79 cells.

Abstract
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.
AuthorsMingxing Wu, Haibo Xiong, Hongmi Zou, Meng Li, Pan Li, Yu Zhou, Yan Xu, Jia Jian, Fengqiu Liu, Hongyun Zhao, Zhigang Wang, Xiyuan Zhou
JournalActa biomaterialia (Acta Biomater) Vol. 70 Pg. 211-226 (04 01 2018) ISSN: 1878-7568 [Electronic] England
PMID29452275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Contrast Media
Topics
  • Animals
  • Cell Line, Tumor
  • Contrast Media (chemistry, pharmacology)
  • Female
  • Genetic Therapy (methods)
  • Humans
  • Lasers
  • Mice
  • Mice, Nude
  • Nanoparticles (chemistry)
  • Neoplasms, Experimental (diagnostic imaging, metabolism, therapy)
  • Photoacoustic Techniques
  • Retinoblastoma (diagnostic imaging, metabolism, therapy)
  • Transfection (methods)
  • Ultrasonography
  • Xenograft Model Antitumor Assays

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