Adjuvant Effect Of Ultrasound Combined With Targeted Nanobubbles On Chemotherapy For Mouse Breast Cancer

Objective To study the adjuvant chemotherapy effect of ultrasound combined with targeted neuropeptide（NPY）Y₁receptor-mediated nanobubbles on mouse breast cancer.Methods（1）The four types of bubbles related to experiments were microbubbles（MBs）,targeted microbubbles（MBs-NPY）,nanobubbles（NBs）,and targeted nanobubbles（NBs-NPY）.Then check the bubbles size and the grafting rate of the targeted bubbles.（2）Subcutaneous injection of 4T1 mouse breast cancer cells to construct a tumor model,and when the tumor volume increased to 60-80mm³,randomly divided into 7 groups（6 groups each）:Blank control group（C group）,Doxorubicin group（group D）,Ultrasound combined with doxorubicin group（DU group）,Ultrasound microbubble combined with doxorubicin group（DUUM group）,Ultrasound targeted microbubbles combined with doxorubicin group（DUTUM group）,Ultrasound nanobubble combined with doxorubicin group（DUNM group）,Ultrasound targeted nanobubbles combined with doxorubicin group（DUTNM group）.Depending on the group,different treatments were given once every 2 days for a total of 3times.After the treatment,evaluate the adjuvant effect of DUTNM group on mouse breast cancer chemotherapy,mainly by measuring the tumor volume,weight of mouse,observation of mouse survival and obtaining important organs（liver,spleen,kidney,heart,lung）andtumor tissue sections in each group.Results The four types of bubbles were uniform in size and spherical in shape,and the average particle size of nanobubbles and microbubbles were200-300nm and 1-3μm,respectively.The grafting rate of PNBL-NPY₁（Ligand mediated by neuropeptide Y₁receptor）and nanobubbles was 75%,the grafting rate of PNBL-NPY₁and microbubbles was 80%.（2）On the 22nd day after the treatment,after ultrasound combined with bubbles adjuvant chemotherapy,the tumor volume of mouse were smaller than that of the only chemotherapy group.the tumor volume in the DUTNM group（310.5±35.5 mm³）was smaller than that in the DUNM group,the difference was statistically significant（p<0.01）;the tumor volume in the DUTNM group was smaller than that in the DUTUM group（403.8±32.0 mm³）,the difference was statistically significant（p<0.05）;the tumor volume in the DUTUM group was smaller than that in the DUUM group（480.1±31.5 mm3）,the difference was statistically significant（p<0.05）.Among the tumor tissue sections,the degree of tumor cellular swelling,nuclear pyknosis and nuclear karyorrhexis in the DUTNM group were obvious,at the same time,the survival of this group of mouse was prolonged.Conclusions Ultrasound combined with microbubbles can improve the chemotherapy effect of mouse breast cancer tumors and inhibit tumor growth.Among them,nanobubbles targeted by neuropeptide Y1 receptor are the best.