Polypyrrole-coated phase-change liquid perfluorocarbon nanoparticles for the visualized photothermal-chemotherapy of breast cancer

Abstract A theranostic nanoplatform (DTX/PFH@PPy-FA) for multi-modal imaging-guided photothermal-chemotherapy has been constructed. Lipid-perfluorohexane (PFH) nanodroplet loaded with docetaxel (DTX) was coated with a polypyrrole (PPy) shell. Then the folic acid (FA) molecule with active tumor-targeting function was modified on the surface of PPy shell. Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces ultrasound imaging effect. The results of photothermal experiment and imaging experiment confirmed that the obtained DTX/PFH@PPy-FA possessed good photothermal, photoacoustic imaging and ultrasound imaging effects in vitro and in vivo . The results of in vitro cell experiments showed that DTX/PFH@PPy-FA had a active targeting ability to tumor cells, and its photothermal-chemotherapy synergistically inhibited the proliferation of tumor cells. In vivo study on 4T1-bearing BALB/c mice indicated that the photothermal-chemotherapy of DTX/PFH@PPy-FA not only effectively inhibited the growth of 4T1 breast cancer, but also inhibited lung metastasis. This multifunctional nanoparticle is expected to become a new nanoplatform for the visualized photothermal-chemotherapy of cancer. Statement of Significance In this work, we presented a multi-modal imaging-guided photothermal-chemotherapy theranostic nanoplatform (DTX/PFH@PPy-FA) for visualized treatment of breast cancer. The docetaxel (DTX) loaded perfluorohexane (PFH) nanodroplets (DTX/PFH@SPC) were firstly prepared and then coated with polypyrrole shell (PPy). Then, PEGylated folic acid was covalently modified to obtain the folate-targeted multifunctional nanoparticle (DTX/PFH@PPy-FA). Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces good ultrasound imaging effect. The PPy shell also imparts photoacoustic imaging characteristics to the nanoparticles. Experimental results show that our prepared DTX/PFH@PPy-FA possesses folic acid-mediated tumor targeting ability, ultrasound and photoacoustic imaging, and photothermal-chemotherapy synergistic effect. This multi-functional nanoparticle is expected to become a new platform for the visualized photothermal-chemotherapy of breast cancer.