Objective To radiolabel hyperbranched polymer(HG)-modified liquid metal nanodro-plet(LMND)@HG with 177 Lu,and explore the radiotherapy sensitization effect on anti-breast cancer thera-py.Methods The ultrasonication method was used to prepare LMND@HG,and then 177LuCl3 was mixed with LMND@HG to label 177Lu by alloying reactions.The labeling rate,plasma stability and cytotoxicity of 177Lu-LMND@HG were detected.Xenograft mouse model of breast cancer was constructed,and the tumor inhibition test was performed by an intratumoral injection.The tumor progression was monitored by in vivo imaging system.The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluo-rescence assays.One-way analysis of variance,repeated measures analysis of variance,and the least signifi-cant difference t test were used to analyze the data.Results 177 Lu was successfully labeled to LMND@HG with a high labeling efficiency＞95％.The product did not require further purification and the plasma radiochemi-cal purity was still higher than 95％after 5 d.The cytotoxicity test showed that a dose of 888 kBq(40 mg/L)177Lu-LMND@HG had obvious toxicity to 4T1 cells,which was significantly lower than 177LuCl3(cell viabil-ities:(16.48±7.81)％vs(85.77±8.87)％;F=77.81,t=11.73,P＜0.001)and LMND@HG((46.53±5.75)％;t=6.20,P＜0.001).The biological distribution results showed that177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection.The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl3(tumor volume:(222.66±97.70)vs(789.13±245.04)mm3;F=18.55,t=4.29,P=0.005).Invivo opti-cal imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly in-hibited the tumor growth.Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break,and suppressed the tumor growth by inhibiting cell proliferation and an-giogenesis.Conclusions A novel 177Lu-liquid metal-based reactive oxygen species(ROS)radiation sensi-tizer is successfully prepared in this study.The preparation method is efficient and convenient,and the prod-uct has high stability.177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.
Breast neoplasmsIsotope labelingLutetiumRadiotherapyReactive oxygen spe-ciesTumor cells,culturedMice,nudeOptical imaging
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