Effects And Mechanisms Of Quantum Dots-RGD On Photodynamic Therapy Of Pancreatic Cancer

Pancreatic cancer is a common malignant tumor of the digestive tract,with the characteristics of latent,high degree of malignancy,and poor prognosis.Pancreatic cancer treatment is currently based on surgery,supplemented by a comprehensive treatment of chemotherapy.Photodynamic therapy(PDT)is the use of light to stimulate cancer cells within the photosensitizer to produce high cytotoxic singlet oxygen,which play a role in killing cancer cells.PDT has the advantages of slight side effects,no resistance,and can be used repeatedly.In the previous experiments,we have demonstrated the cell-killing effect of RGD conjugated quantum dots(QDs-RGD)mediated photodynamic therapy on pancreatic cancer cells.This study was designed to investigate the effect of QDs-RGD on PDT in pancreatic cancer-bearing animal models and to analyze whether its own toxicity affects animals.The aim of the study was to evaluate whether the QDs-RGD itself is toxic to animals and investigate the photodynamic therapy effects induced by QDs-RGD on pancreatic cancer bearing animal models.Part I Safety analysis of QDs-RGD in animal model of pancreatic cancerAims: To show the immediately changes of distribution of the nanomaterials in the bodies of mice,and evaluate whether the QDs-RGD is toxic to animals by comparison of different doses and injection methods.Methods: Different dosages(5 pmol,25 pmol and 50 pmol)and injection methods(intratumoral injection,tail vein injection and QDs injection)were used to observe the distribution of nanomaterials in pancreatic cancer bearing animal models.The toxicity of the nanomaterials was evaluated by evaluating the histopathological sections of the mice,measuring the cadmium concentration of each organ from the dissected organs,and observing the long-term survival status of the animals.Results: Compared with the traditional method of tail vein injection,the method of intratumoral injection of QDs-RGD is more sufficient to show fluorescence efficiency.It can ensure the tumor area to maintain long-time and efficient fluorescence intensity.The in vivo imaging analysis suggested that a small dose(5 pmol)of QDs-RGD could exert a high-efficient fluorescence radiant over a long period of time(5 hours).In this experiment,by analyzing the related histopathological slices,cadmium ion concentrations and long-time observations of the nude mice without the occurrence of weight loss,lack of energy or other poisoning performance,we found that the nanomaterials would not cause serious damages or side effects to the animals.And the distribution of cadmium in animals is consistent with the in vivo fluorescence imaging.Conclusions: Through the in vivo fluorescence imaging experiments,nano-materials are safe and reliable without causing serious damages to animals or other side effects.The method of intratumoral injection ensures that the QDs-RGD maintains in the animal tumor area.The experiment provides a dose basis and safety assurance for the subsequent QDs-RGD-mediated photodynamic therapy.Part II The effects of QDs-RGD induced photodynamic therapy on pancreatic neoplasmAims: The experiments are conducted to verify the photodynamic therapy effects mediated by QDs-RGD on pancreatic cancer in animals.Methods: The changes of fluorescence distribution in pancreatic cancer-bearing animal model were observed by IVIS system.The procedure was to determine the most appropriate injection dose and irradiating time after the intratumoral injection of QDs-RGD.For the purpose of improving the effect of PDT treatment,photodynamic therapy was performed using intratumoral irradiation.At the same time,two control groups(intratumoral injection + extracorporeal irradiation / intratumoral irradiation alone)were conducted to compare the effects of different treatments on animal.The difference of the three groups indicated the effectiveness of the intratumoral injection+ intratumoral irradiation.The experiment proved that the most effective method of PDT treatment is intratumoral injection + intratumoral irradiation method.Results: Intratumoral injection of 5 pmol QDs-RGD can make nanomaterials maintain in the tumor area for long time(1 hour)with efficient fluorescent effect.The results suggest that intratumoral injection of 5 pmol was the appropriate photodynamic therapy dose,and the appropriate irradiating time should be within 1 hour post injection.Intratumoral injection + intratumoral irradiation method can significantly improve the effect of photodynamic therapy.After prolonged observation,the growth of tumor volume in the experimental group was significantly inhibited.Pathological analysis results suggest that there are a large number of necrotic tissue and inflammatory cells in the dissected tumor tissues,while the control group did not show significant tumor growth inhibition.Conclusions: In animal experiments,QDs-RGD-mediated photodynamic therapy can kill pancreatic cancer cells.And the method of intratumoral injection and intratumoral irradiation can play a significant anti-cancer effect by less injection dose.