The Construction And Application Of Phage-based Nanotheranostics For Cancer Radiochemotherapy

Cancer is threatening human health dreadfully over the world.The current cancer treatments in clinical practice mainly employ radiotherapy and chemotherapy,but their therapeutic effect is limited by the radiation dose and the toxicity of chemotherapy drugs.In addition,the combined treatment of these two methods can often be ineffective because it cannot accurately affect the tumor in the same area.Thus,there is an urgent need to provide a targeted strategy for exerting maximal synergistic chemoradiotherapeutic effect with minimal side effects.Thanks to the introduction of the integrated concept of cancer theranostics and the advancement of nanomedicine,nanotheranostics that integrate diagnosis and treatment functions open up a new path for early diagnosis and collaborative treatment of cancer.Among them,the protein nanocage as a natural nanocarrier has good biocompatibility,unique three-dimensional structure and functions,shows great prospect in cancer theranostics.In this study,we cleverly used the natural cage-like structure of Qβbacteriophage nanoparticles to design and synthesize a new R-QβAu@DOX nanotheranostics that is simultaneously loaded with chemotherapy drugs doxorubicin and radiosensitized gold nanoclusters for the combined radiotherapy and chemotherapy of hepatocellular carcinoma.Studies have shown that our R-QβAu@DOX can overcome the previous problem that the chemotherapy drug doxorubicin easily aggregates with gold nanoclusters as well as effective release its internal loaded Doxorubicin under X-ray excitation through the radiosensitization effect mediated by surface-coupled gold nanoclusters.In vitro cell experiments indicated that this nanotheranostics can effectively enhance the uptaken of tumors with the help of surface targeting ligands,and the greatest cell DNA destruction and tumor cell killing under X-ray irradiation.In vivo studies,R-QβAu@DOX demonstrated excellent CT imaging capabilities due to the X-ray attenuation ability of Au,what’s more,with the help of reasonable nanostructures,the nanocarriers can enrich in the tumor area in vivo by the EPR effect and active targeting,and then the small-sized AuNCs can be quickly metabolized from urine,which achieves the balance between the nanocarrier EPR effect and the rapid metabolism in the body.Finaly,because the chemotherapy drugs,radiotherapy sensitizers and exogenous X-ray act on the same area of the tumor synchronously,R-QβAu@DOX nanotheranostics in HepG2 tumor model achieves highly effective tumor suppression effect.In summary,we have constructed a novel R-QβAu@DOX nanotheranostics with high biosafety and tumor suppression effects which provides an important reference for medical conversion of nanobiomaterials.