2023, Vol. 27 ›› Issue (12): 1863-1869

Near infrared photoresponsive nanoparticles loaded with LXR agonists for photothermal immunotherapy

Gan Tian1, Wang Wenyuan1, Yan Shujin2, Hao Lan3, Ran Haitao3, Wang Zhigang3, Xia Jizhu1   

Abstract: BACKGROUND: Breast cancer seriously threatens the physical and mental health of women around the world. The development of early accurate diagnosis and efficient treatment strategies for breast cancer is crucial to improve the chances of survival of patients.
OBJECTIVE: To prepare new multifunctional targeted nanoparticles (PLGA-IR780-RGX104) containing IR780 and LXR agonist (RGX104), and to explore the effect of basic physicochemical properties, photoacoustic signal in vitro, and photothermal therapy combined with immunotherapy for breast cancer.
METHODS: (1) Using poly(lactid-co-glycolide) as carrier, new multifunctional targeted nanoparticles (PLGA-IR780-RGX104) were prepared by double emulsification method, and their physicochemical properties and effect of photoacoustic imaging in vitro were demonstrated. (2) Mouse breast cancer cells 4T1 in logarithmic growth phase were taken and cultured in five groups: PBS group, PBS+laser irradiation group, PLGA-IR780-RGX104 group, PLGA-RGX104+laser irradiation group, and PLGA-IR780-RGX104+laser irradiation group. Each group contained 40, 50, 60, 70, and 80 mg/L mass concentrations. After culturing for 24 hours, the cell viability was detected by Cell Count Kit-8 assay. (3) 4T1 cells and bone marrow cells were co-cultured in a Transwell chamber under the stimulation of granulocyte-macrophage colony-stimulating factor and were divided into seven groups: 4T1 cell-free group, PBS group, free RGX104 group, PLGA-IR780 group, PLGA-IR780+laser irradiation group, PLGA-IR780-RGX104 group, and PLGA-IR780-RGX104+laser irradiation group. After 6 days of culture, flow cytometry was used to evaluate the number of myeloid-derived suppressor cells in bone marrow cells of each group.
RESULTS AND CONCLUSION: (1) The prepared new multifunctional targeting nanoparticles were uniform in dispersion and size. The individual nanoparticle was spherical. The average particle size was 275.00 nm and the average potential was -12.00 mV. The encapsulation rates of IR780 and RGX104 were 93.47% and 84.30%, respectively. The drug loading of IR780 and RGX104 was 4.20% and 6.68%, respectively. After laser irradiation, the release rate of RGX104 increased significantly. The nanoparticles exhibited an obvious photoacoustic signal, which got stronger as the concentration increased. (2) With the increase of the mass concentration of the nanoparticle solution, the cell viability in the PLGA-RGX104-IR780+laser irradiation group decreased sequentially, and was significantly lower than that in the other four groups at the same mass concentration (all P < 0.000 1). (3) The number of myeloid-derived suppressor cells in the PLGA-IR780-RGX104+laser irradiation group was less than that in the PBS group, PLGA-IR780+laser irradiation group, and PLGA-IR780-RGX104 group (all P < 0.000 1), and was comparable to the 4T1 cell-free group and the free RGX104 group (P > 0.05). (4) The results showed that the new multifunctional targeted nanoparticles containing IR780 and LXR agonist (RGX104) could be used in photoacoustic imaging guided photothermal therapy combined with immunotherapy of breast cancer.
Key words: nanoparticle, myeloid-derived suppressor cell, LXR agonist, immunotherapy, photothermal therapy, combination therapy, photoacoustic imaging