¹³¹I Labeled Polydopamine Nano Drug Delivery System For Radionuclide-guided Tumor Radiotherapy And Chemotherapy

Objective:Nanoparticles and nanocomposites are widely used in various applications such as biomedicine,textiles,cosmetics,agriculture,optics,food packaging,and optoelectronics.Especially in the field of cancer treatment and diagnosis in biomedicine,it has great potential for development.Compared with inorganic nanomaterials,organic nanomaterials have a significant advantage in biocompatibility,which also provides favorable conditions for the clinical transformation of organic nanomaterials.In the meanwhile,the treatment of tumor by single means has limitation on the curative effect and side effect,and the combination therapy is used in clinic.Therefore,developing a multifunctional nanomaterials for the combination therapy of the cancer based on biocompatible organic nanomaterials has attracted great attention in these years.Based on these theory,this study providesapromisingpolymer-basedplatformtorealizeimaging-guided radioisotope/chemotherapy combination cancer treatment in future clinic application.Materials and Methods:In this study,polydopamine（PDA）nanoparticles were synthesized with uniform sizes by a aqueous phase oxidation reaction and then coated with PEG.PEGylated PDA nanoparticles can effectively load two different drugs including Sanguinarine（SAN）and Metformin（MET）,as well as radionuclides ¹³¹I in one system because of its excellent surface modification ability.This nanoparticle drug carrier is used in combination therapy for tumor chemo-radiotherapy under the guidance of radionuclide imaging.Results:We found that PEGylated PDA nanoparticles（PDA-PEG）exhibited well stability in different solutions.PDA-PEG nanoparticles can effectively load with two anti-tumor drugs Sanguinarine（SAN）and Metformin（MET）,as well as radionuclides ¹³¹I for follow-up in vitro and in vivo imaging therapy.For in vitro experiment,PDA-PEG nanoparticles exhibited great ingestion ability and no obvious toxicity to 4T1 cancer cells.Hence,SAN、MET and ¹³¹I co-loaded PDA-PEG showed significant cytotoxicity compared with that of PDA-PEG-SAN or ¹³¹I-PDA-PEG alone.For in vivo experiment,¹³¹I labeled PDA-PEG(¹³¹I-PDA-PEG)exhibited an excellent contrast agent for radionuclide imaging and relative long-term blood circulation time and high tumor uptake.This PEGylated PDA nanoparticles significantly inhibite the growth of tumor in mice by combination treatment.At the same time,metformin loaded in PDA-PEG nanoparticles is further improved the oxygen microenvironment of the tumor to enhance the radiotherapy effect.Conclusion:In this work,we designed a multifunction biocompatible drug delivery system for co-loading of both radionuclides and anticancer drug to radionuclide imaging guided combined therapy.Therefore,it is hoped that this drug delivery system would provide valuable reference for future tumor diagnosis and treatment.