A multifunctional-targeted nanoagent for dual-mode image-guided therapeutic effects on ovarian cancer cells

Abstract

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
• ulta-sound
• photo-sonodynamic therapy

Acknowledgments

The authors are grateful to Dr Ronald X. Xu (Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui, China) for technical advice, Dr Pan Li and Lan Hao (Institute of Ultrasound Imaging, Second Hospital of Chongqing Medical University, and Chongqing, China) for technical advice on dual-mode imaging, and Dr Tinghe Yu (Director of Key Medical laboratory of Obstetrics and Gyne-cology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China) for the generous support of the experimental facilities. This study was supported by the Natural Science Foundation of China (81572558, 81630047, 31630026) and Natural Science Foundation of Chongqing (cstc2018jcyjAX0103, cstc2018jcyjAX0223).

Author contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.