Radionuclide Labeled Nanocarrier For Imaging Guided Combined Radionuclide,Sonodynamic,and Photothermal Therapy Of Pancreatic Tumours

Objective:A polydopamine-modified Au nanostar was constructed and then co-loaded with the acoustic sensitizer protoporphyrin and labeled radionuclides for preliminary evaluation in mouse pancreatic cancer cells and animal tumor models to guide the precise diagnosis and treatment of pancreatic cancer.Methods:In this study,Au nanostars(AN)were synthesized by wet chemical method,and a layer of polydopamine(PDA)and loaded acoustic sensitizer protoporphyrin(IX)were modified on its surface to obtain AN@D/IX.Then the nucleophiles 131I and 99mTc were labeled on AN@D/IX by chloramine-T method and stannous chloride(SnCl2)reduction method,respectively,and their labeling yields and stability were examined.In vitro experiments were performed to assess the toxicity and therapeutic effects of 131I-AN@D/IX on mouse pancreatic cancer cells BxPC-3 using CCK-8 reagent.Then 99mTc-AN@D/IX was injected intratumorally and the tumor uptake at different time points was observed by Single-Photon Emission Computed Tomography(SPECT imaging).Results:Nanocarriers labeled with both diagnostic(99mTc)and therapeutic(131I)nuclides have high radiolabeling efficiency and radiochemical stability.After intra-tumor administration,SPECT imaging showed that the nanocarriers labeled with nuclides were mostly retained inside the tumor compared to free nuclides.In addition,the carrier can be used for Photothermal Therapy(PTT)with near-infrared laser and Sonodynamic Therapy(SDT)with high penetration depth of ultrasound triggering the generation of reactive oxygen species by Sonosensitizer IX.Finally,radionuclide therapy(RNT)-SDT-PTT three-modal combination therapy was realized,which significantly improved the therapeutic effect on pancreatic cancer.Conclusion:This study proposes an effective combined radionuclide therapy regimen for cancer that combines three widely used cancer treatment strategies,RNT-SDT-PTT,and offers hope for future clinical translation of cancer treatment.