Effect Of Plectin-1 Spectific Binding Peptide Modified Gold Nanoparticles Cooperating With Radiotherapy Of PDAC

Pancreatic cancer is a common malignant tumor.The incidence and mortality of the disease are almost the same,and the mortality rate accounts for 98% of the annual incidence.It is called the "king of cancer".Pancreatic Ductal Adenocarcinoma(PDAC)is the most common and deadly pancreatic cancer,accounting for more than90% of pancreatic cancer.PDAC is an aggressive tumor with early symptoms,atypical,aggressive,malignant.High degree,insensitive to current major treatments,poor prognosis,and more than 80% of patients are in advanced stage of cancer when diagnosed with pancreatic cancer,only 10%-15% of patients can be radically diagnosed Excision,the 5-year survival rate is also only 1%-5%.Radiation therapy is a more effective method for the treatment of malignant tumors.Radiotherapy has a significant effect on local control and analgesia of pancreatic cancer.However,there are certain defects in the PDAC radiation therapy.The pancreas is adjacent to the gastrointestinal tissue and is in patients with pancreatic cancer.In the course of radiotherapy,high doses of radiation cannot be specifically delivered to the location of pancreatic tumors,while low doses of radiotherapy have limited efficacy in the treatment of pancreatic ductal adenocarcinoma,resulting in radiotherapy not widely used in patients with clinical pancreatic cancer..In order to enhance the radiosensitivity of tumors and reduce the damage to normal cells,sensitizers are often used clinically to enhance the killing effect of tumors.Gold nanoparticles(Au NP)have been used for cancer therapeutics as radiosensitizers due to their strong absorption capacity for X-rays.However,it's neccassary to enhance the complex level of surface modification of Au NP so as to achieve efficacy and limit off-target toxicity.In this study,we described a novel conjugate complex consisting of the peptide PP for targeting plectin-1 specifically expressed on the pancreatic cancer cell membrane and Au NP,termed Au NP-PP,to be used for radioactive therapy of pancreatic cancer in vitro and in vivo.The results indicate that Au NP-PP greatly increased the targeting efficiency and induced apoptosis in treated pancreatic ductal adenocarcinoma cells and tumors along with relevant low-energy X-ray irradiation of 6MV in the dose of 2Gy(RF)when compared to that of unmodified Au NP.More importantly,extensive histopathological examination did not reveal evidence of acute or chronic injury of Au NP or Au NP-PP intraperitoneally injected mice up to six weeks despite the presence of X-ray field exposure.Taken together,Au NP-PP combined with low-energy X-rays can more effectively inhibit the growth and induce the apoptosis of PDAC than that of uncoated Au NP.The delicate gold nanoparticle-peptide hybrids provides a novel strategy to enhance the radiotherapy efficiency in the most challenging PDAC treatment and also provide a theoretical basis for the clinical application of Au NP-PP in PDAC.