Tumor-targeting nanoparticles with phase transition for multimodal-imaging-guided sonodynamic therapy in vitro

Objective 　To develop tumor-targeted multifunctional nanoparticles with phase transition, and to investigate their multimodal imaging, delivery efficiency on tumor cells and efficacy of sonodynamic therapy (SDT). Methods 　IR780 and perfluoropentane (PFP) based liposome (Lip-PFP-IR780) nanoparticles were synthesized by an emulsion strategy. The characteristics of these nanoparticles were determined. Multimodal imaging ability of Lip-PFP-IR780 nanoparticles was evaluated by ultrasound (US), photoacoustic (PA) and fluorescence (FL) imaging in vitro. The delivery efficiency of Lip-PFP-IR780 to 4T1 cancer cells (mouse breast cancer cells) was evaluated by the laser scanning confocal microscope and flow cytometry. In vitro sonodynamic properties of these nanoparticles was evaluated by Singlet Oxygen Sensor Green (SOSG) assay and CCK-8 assay. Results 　These nanoparticles presented homogenized size distribution. The average diameter was 338.5±124.2nm and zeta potential was –27.6±2.4mV. Meanwhile, the entrapment efficiency of IR780 was calculated as 91.6%. In vitro, after low intensity focused ultrasound (LIFU) radiation, the Lip-PFP-IR780 nanoparticles undergone phase transformation and could be used for US contrast imaging. The PA signal intensity of nanoparticles increased along with the increase of the concentrations. The nanoparticles also could be used for near-infrared fluorescence imaging in vitro. The binding efficiency of targeting nanoparticles in 4T1 cells was much higher than non-targeted nanoparticles (P＜0.05). During SDT, it would cause cell death due to singlet oxygen (1O2) produced after the LIFU irradiation. As expected, the 4T1 tumor cells were ablated and the cell viability in LIFU irradiation groups significantly decreased compared with the groups without LIFU irradiation (P＜0.05). Conclusion 　Tumor-targeted multifunctional nanoparticles with phase transition were successfully constructed for multimodal-imaging-guided SDT. DOI: 10.11855/j.issn.0577-7402.2018.10.03