International Journal of Nanomedicine (Jan 2019)
A multifunctional-targeted nanoagent for dual-mode image-guided therapeutic effects on ovarian cancer cells
Abstract
Chunyan Chen,1 Jiangchuan Sun,1 Shuning Chen,1 Yujiao Liu,1 Shenyin Zhu,2 Zhigang Wang,3 Shufang Chang1 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; 2Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China Purpose: Nanomedicine has emerged as a novel therapeutic modality for cancer treatment and diagnosis. Lipid–polymer hybrid nanoparticles (LPHNPs) are core–shell nanoparticle (NP) structures comprising polymer cores and lipid shells, which exhibit complementary characteristics of both polymeric NPs and liposomes. However, it is difficult to wrap perfluoropentane (PFP) into core–shell NPs in the existing preparation process, which limits its application in the integration of diagnosis and treatment.Methods: The folate-targeted LPHNPs-loaded indocyanine green/PFP-carrying oxygen (TOI_HNPs) using a combination of two-step method and solution evaporation technique for the first time. The essential properties and dual-mode imaging characteristics of developed NPs were determined. The cellular uptake of TOI_HNPs was detected by confocal microscopy and flow cytometry. The SKOV3 cell viability and apoptosis rate were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. The ROS was demonstrated by fluorescence microplate reader and the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and IL-6 was detected by Western blot.Results: TOI_HNPs showed spherical morphology with particle size about (166.83±5.54) nm and zeta potential at -(30.57±1.36) mV. It exhibited better stability than lipid NPs and higher encapsulation efficiency as well as active targeting ability than poly (lactic-co-glycolic acid) (PLGA) NPs. In addition, the novel NPs could also act as the contrast agents for ultrasound and photoacoustic imaging, providing precision guidance and monitoring. Furthermore, TOI_HNPs-mediated photo–sonodynamic therapy (PSDT) caused more serious cell damage and more obvious cell apoptosis, compared with other groups. The PSDT mediated by TOI_HNPs induced generation of intracellular ROS and downregulated the expression of HIF-1α and IL-6 in SKOV3 cells.Conclusion: This kind of multifunctional-targeted nanoagent may provide an ideal strategy for combination of high therapeutic efficacy and dual-mode imaging guidance. Keywords: core-shell nanoparticle, phase transformation, photoacoustic imaging, laser, ultasound, photo-sonodynamic therapy
