Design And Synthesis Of Nanotheranostic Agents Based On Co-P For Tumor Diagnosis And Therapy

Malignant tumor is a serious threat to human health.Improving its diagnostic accuracy and therapeutic effect can effectively reduce the mortality of tumor patients.Traditional diagnosis and therapy methods of tumor have their own limitations.The emerging nanotheranostic agents,intergrating diagnostic and therapeutic functions into single system,provide a new platform for tumor diagnosis and therapy.In this study,we have constructed new multifunctional nanotheranostic agents based on Co-P nanocomposites for magnetic resonance imaging（MRI）and therapy of tumor.The study included two parts as follows:1.Co-P nanocomposites were synthesized by thermal decomposition,and then coated by biocompatible polydopamine（PDA）.A novel nanotheranostic agent（Co-P@PDA-DOX）has been successfully constructed by loading doxorubicin（DOX）on the surface of the Co-P@PDA viaπ-πstacking.Co-P core enabled nanotheranostic agent to apply for both T₂ MR imaging and photothermal therapy（PTT）owing to its strong intrinsic magnetic properties and photothermal conversion performance.After coating PDA shell,Co-P@PDA-DOX possessed the enhanced PTT effect and pH/temperature-responsive on-demand drug release ability,achieving T₂ MRI-guided chemo-photothermal synergistic therapy.Such synergistic therapy not only greatly improved the anti-tumor therapy effect,but also avoided the damage to normal tissues,thereby reducing the toxicity and side effects and averting drug resistance.The uniform size and morphology as well as good stability of Co-P@PDA-DOX were confirmed by characterizations.Its good abilities of drug loading and pH/temperature-responsive drug release were further proved,and excellent photothermal conversion performance offered it great potential for PTT in vitro and in vivo.Its excellent T₂ MR imaging performance was verified by in vivo and in vitro MR imaging tests.A series of experiments in vitro and in vivo including cell imaging,cell viability analysis and inhibition of tumor growth further proved the low biotoxicity,good biocompatibility and outstanding anti-tumor treatment effect of this nanotheranostic agent.In summary,Co-P@PDA-DOX has potential application prospects in T₂ MRI-guided chemo-photothermal synergistic therapy.2.We constructed another nanotheranostic agent（Co-P@mSiO₂@DOX-MnO₂）with Co-P as core,mesoporous silica as shell,and manganese dioxide（MnO₂）nanosheets as cap,which has been employed for pH-responsive T₁/T₂ dual-mode MRI-guided chemotherapy and PTT synergistic anti-tumor therapy.Co-P core enabled nanotheranostic agent to be used for both T₂ MR imaging and PTT.Mesoporous silica shell was employed as good carrier for loading chemotherapeutic drugs owing to its mesoporous structure.In the acidic environment of tumors,MnO₂ cap could be dissolved into Mn²⁺ions,which not only realized pH-responsive on-demand drug release but also activated T₁ MRI contrast enhancement.Structure characterization and toxicity analysis were employed to comfirm the uniform morphology and size as well as good biocompatibility of Co-P@mSiO₂@DOX-MnO₂.Its superior pH-responsive drug release ability and photothermal conversion ability were verified by drug releasing and photothermal properties tests.In vivo and in vitro MR imaging and anti-tumor treatment tests proved its excellent T₁/T₂ dual-mode MR imaging and anti-tumor treatment effect.In a word,Co-P@mSiO₂@DOX-MnO₂ has potential to serve as theranostic agent for pH-responsive T₁/T₂ dual-modality MRI-guided chemo-photothermal synergistic therapy.Compared with Co-P@PDA-DOX,Co-P@mSiO₂@DOX-MnO₂ could serve as multi-mode MR imaging contrast,providing further comprehensive details and accurate information for tumor diagnosis.Furthermore,the drug release efficiency was also significantly improved,which increased the anti-tumor therapy efficiency.We successfully designed and synthesized two kind of nanotheranostic agents（Co-P@PDA-DOX and Co-P@mSiO₂@DOX-MnO₂）,and applied them in biomedical field for the first time.They exhibited favorable biocompatibility,excellent tumor diagnostic and therapuetic effects,realizing the synchronization of tumor diagnosis and therapy as well as providing theoretical and practical basis for the future clinical application of nanotheranostic agents.