A Versatile Nanoplatform For Multimodal Image-mediated Breast Cancer Therapy

Breast cancer has the highest incidence among female cancer diseases in the world,which heavily threatens women’s healthy.If early diagnosis can be made,the survival rate of breast cancer can be significantly improved,so the early diagnosis and treatment of breast cancer is particularly important.In the aspect of treatment,there are mainly surgical resection,chemoradiotherapy and so on.However,there are some negative problems in surgery,such as overtreatment,wound infection,easy recurrence and metastasis.Chemoradiotherapy can also cause side effects,resulting in a general decline in the quality of life of patients.In terms of diagnosis,medical imaging methods such as X-ray and CT,MRI,ultrasound imaging are commonly used,but these still can’t meet the needs of early tumor diagnosis,and there are often missed diagnosis,thus delaying treatment.At present,with the rapid development of targeted molecular image contrast agent and the integrated mode of diagnosis and treatment,it is one of the hotspots and difficulties in clinical research to realize early diagnosis,early treatment and cooperative treatment of tumor.1.Objective:To design a kind of nano-particle T-lipos-CPAuNCs,with photothermal conversion,rapid uptake by tumor cells,synchronous anti-inflammatory and anti-metastasis therapy and multi-mode imaging under the action of near-infrared light,and has good biosafety to achieve accurate localization of breast cancer and improve the therapeutic effect.2.Methods:Gold nanocage liposomes with targeting function were obtained by silver-gold replacement reaction and thin film extrusion method.The morphology of gold nano-cage liposomes was observed by transmission electron microscope（TEM）.We also demonstrated the tumor targeting ability of T-lipos-CPAuNCs in vivo and in vitro,as well as photoacoustic/ultrasound imaging and efficient photothermal therapy of tumors.At the same time,the drug release of celecoxib in T-lipos-CPAuNCs and the characterization of anti-inflammatory activity in vivo and in vitro were investigated.3.Results:T-lipos-CPAuNCs nanoparticles with a particle size of about 220 nm were successfully constructed.Under electron microscope,the morphology is uniform and the dispersion is good.At the same time,T-lipos-CPAuNCs can effectively gather to the tumor site in vivo and in vitro,and has good ultrasound/photoacoustic imaging effect in liquid phase characterization in vitro and in mouse breast cancer.In cell and animal experiments,it can effectively inhibit tumor cells and alleviate inflammation.4.Conclusions:We have developed a cRGD targeted tumor peptide liposome containing gold nanocage（T-lipos-CPAuNCs）loaded with anti-inflammatory drug celecoxib Cel and ultrasound contrast agent perfluorohexane PFH for efficient photothermal therapy of cancer PTT,to inhibit inflammation and hyperthermia to enhance photoacoustic and ultrasound imaging.Compared with unmodified cRGD nanoliposomes,T-lipos-CPAuNCs showed better tumor targeting ability in vivo and in vitro.Under the irradiation of 793 nm near infrared laser,T-lipos-CPAuNCs produced heat to destroy cancer cells,and celecoxib Cel released by T-lipos-CPAuNCs could reduce the inflammatory response induced by PTT.At the same time,high temperature AuNCs could stimulate the liquid-gas conversion of PFH for ultrasonic imaging,and convert light energy into sound energy for photoacoustic imaging,which is of great help to the treatment evaluation of deep tumors.We believe that T-lipos-CPAuNCs will be a powerful weapon for us to guide tumor PTT and alleviate inflammatory response by imaging.This work has successfully provided ultrasonic nano-system for photothermal/anti-inflammatory treatment of breast tumors under the guidance of photoacoustic/ultrasonic imaging.Nanoparticles have successfully carried out accurate diagnosis and treatment of breast cancer.It plays an obvious killing and anti-inflammatory effect in the tumor site.