Background
Breast cancer is one of the most serious diseases facing human health. Nanomedicine has conducted extensive research in the diagnosis and treatment of tumors. Nanodrug loading system has significant value in the diagnosis and treatment of breast cancer.
Objective
We designed a novel near-infrared activated therapeutic folate-receptor (FA) targeting IR780-R837-perfluorohexane (PFH) @ polyethylene glycol (PEG) – poly (lactide-co-glycolic acid) (PLGA) nanoparticles (FA-NPs) as a safe and approved material and drug for use. Efficient photothermal therapy can be achieved through laser irradiation. In addition, folate targeted NPs can be activated by near-infrared laser irradiation in specific regions, which leads to rapid release of R837 in the high expression region of folate receptors and ensures higher concentration of R837 in the tumor area, resulting in a synergistic anti-tumor effect of chemical/photothermal therapy. Meanwhile, the nanoparticles can be used as dual-mode contrast agents for photoacoustic and ultrasound imaging.
Methods
FA-NPs nanoparticles were prepared by ultrasonic method and their physicochemical properties were characterized. Evaluate nanoparticles as dual-mode contrast agents in vitro and in vivo using photoacoustic/ultrasound imaging systems. The cytotoxicity of 4T1 breast cancer cells was measured by CCK8 method, and its apoptosis was detected by flow cytometry. The anti-tumor therapeutic effect in vivo was evaluated on the tumor bearing mouse model.
Result
The size of the FA-NPs is 150.4 ± 11.4nm, with a potential of -16.3 ± 3.79mV, exhibiting excellent photothermal effects. FA-NPs can induce rapid release of IR780 through laser irradiation. Through photoacoustic/ultrasound imaging, FA-NPs has demonstrated excellent ability as a dual-mode contrast agent. FA-NPs exhibit the good anti-cancer effects in vitro and in vivo with laser irradiated NPs. The photothermal agents IR780, PFH and R837 are coencapsulated by PLGA. The formed FA-NPs nanoparticles are composed of three components and can be used for near-infrared laser triggered primary tumor photothermal ablation to produce tumor related antigens. When nanoparticles containing R837 are used as adjuvants, they can display vaccine like functions. Combined with checkpoint blockade using anti cytotoxic T lymphocyte antigen-4 (CTLA4), the generated immune response will be able to attack the remaining tumor cells in the mouse body, helping to suppress metastasis. This strategy provides a strong immune memory effect, which can prevent tumor recurrence again after eliminating the initial tumor.
Conclusion
This new type of biocompatible thermal therapy nanoparticle is expected to integrate dual-mode imaging technology, improve treatment efficacy, and provide a promising example for cancer treatment.