Polydopamine As A Biocompatible Multifunctional Nanocarrier For Combined Radioisotope Therapy And Chemotherapy Of Cancer

Objective: The development of nanotechnology will bring a new opportunity for nanomedicine, particularly in diagnosis and treatment of cancer. Nanomaterials with intrinsic unique physical and chemical properties show great potential applications in both diagnosis and treatment of cancer. Inorganic nanomaterials are suffering a huge resistance in the process of clinical transformation due to the existed issues of biological security which usually cannot be neglected in the biomedical field. While biocompatible nanocarriers constructed by organic nanomaterials show great prospects in biomedicine. Currently, using a single method has significant limitations on the treatment effect of cancer, combining different strategies of cancer therapy has been adopted on clinic. Therefore, developing biocompatible and multifunctional nanomaterials for the combination therapy of cancer has attracted great attention gradually in recent years.Materials and Methods: In this work, polydopamine（PDA） nanoparticles were fabricated with uniform sizes by a self-polymerization reaction and coated with PEG. PDA-PEG nanoparticles were then labeled with radionuclide 99 mTc for single photon emission computed tomography（SPECT） imaging or labeled with 131 I for radiotherapy. Moreover, doxorubicin（DOX）, a type of anticancer drug, could also be loaded onto ¹³¹I-PDA-PEG nanoparticles for imaging guided combined chemo-radiotherapy of cancer. The use of this strategy could improve the therapeutic efficiency of cancer at a relatively low dose, meanwhile, decrease the systemic side effects.Results: We found that PEGylated PDA nanoparticles（PDA-PEG） exhibited well stability and biocompatibility in different solutions. Utilizing its intrinsic properties, PDA-PEG nanoparticles could be used as excellent nano-carriers to load anticancer drug of DOX and radionuclides of 99 mTc and 131 I. PDA-PEG themselves induced no obvious toxicity to 4T1 cancer cells even at high concentration（1000 mg/m L）. However, DOX and 131 I co-loaded PDA-PEG showed significant cytotoxicity compared with that of ¹³¹I-PDA-PEG or PDA-PEG/DOX alone. For in vivo experiments, 99 mTc labeled PDA-PEG(^99mTc-PDA-PEG) could be used as an excellent contrast agent for SPECT imaging. After being intravenous injection, ¹³¹I-PDA-PEG/DOX exhibited relative long-term blood circulation time and high tumor uptake via enhance the penetration and retention（EPR） effect, further improving the therapeutic efficiency of cancer. More importantly, ¹³¹I-PDA-PEG/DOX induced no obvious side effects to treated animals at our tested dose in the long run.Conclusions: In this work, we designed a novel drug delivery system based on biocompatible nanomaterial, for co-loading of both radionuclides and anticancer drug to realize imaging guided combined therapy of cancer. More importantly, this drug delivery system could enhance therapeutic efficiency of cancer without rendering significant toxicity to the treated animals. Therefore, it is hoped that this strategy would provide valuable reference on the diagnosis and treatment of cancer in the future.