Albumin Biomimetic Nanocarrier Loading Photothermal Agents And SiRNA Inhibit Lung Metastasis Of Breast Cancer

Breast cancer is "the first killer" of women's health,Metastasis is one of the major causes of death in patients with breast cancer,among which 60-70% of the patients died of the lung metastasis.It's urgent for designing a nanocarrier to delivery drug to inhibit lung metastasis of breast cancer.We designed an albumin biomimetic nanocarrier loading photothermal agents and siRNA inhibit lung metastasis of breast cancer,which was based on the combination of thermotherapy and RNA interference.In the present work,DOPE-SS-R9 was prepared via conjugating R9 to DOPE.DRI nanoparticles loading near infrared dyes(IR780)based on DOPE-SS-R9 and DOPE by self-assembly at mass ratio of 10:1,can compress siRNA through electrostatic interactions(DRI-S)at molar ratio of 9:1.DRI-SH nanoparticles loading photothermal agents and siRNA was prepared with HSA and DRI-S through electrostatic interactions at mass ratio of 4:1.These nanoparticles was prepared and the particle size,Zeta-potential,encapsulation efficiency and the extent of temperature elevation in vitro were investigated.The results showed that the average particle size of DRI?DRI-S and DRI-SH was 36.53nm?71.93nm?100.1nm,Zetapotential was +41.5mV?+30.2mV?+8.16 mV.The encapsulation efficiency of DRI were 97.01%.these nanoparticles can raise the temperature,while the temperature of DRI-SH is above 50 ?,it indicated that the nanoparticles can produce certain effect to treat cancer.DRI?DRI-S?DRI-SH nanoparticles were studied in 4T1 for suppressing metastasis of breast cancer.Cytotoxicity,the cellular uptake and cell migration were investigated.The results showed that these nanoparticles can be uptake effectively,and promote siRNA to escape from lysosomes.DRS and DRSH can knockout twist protein efficiently,the inhibition rate of nanoparticles against cell migration was 60%.After 808 nm NIR laser irradiation,the inhibition rate of nanoparticles against cell migration was increased to 80% significantly.This paper studied biodistribution of DRI?DRI-S?DRI-SH nanoparticles in 4T1 tumor-bearing mice and temperature elevation of tumor by NIR laser irradiation.The results showed that these nanoparticles were distributed mainly in tumor ?liver and lung.The distribution of DRI-SH in the tumor showed 2.5 and 2.7 times than DRI?DRI-S.After 808 nm NIR laser irradiation,the temperature of DRI-SH can reach above 50? to inhibit the growth of tumor.Taken together,Albumin biomimetic nanocarrier loading photothermal agents and siRNA inhibit lung metastasis of breast cancer,which was based on the combination of thermotherapy and RNA interference.