Synthesis Of Cobalt-based Nanotheranostic Agents And Their Applications In Tumor Therapy

Co-based nanotheranostic agents is becoming a superstar in tumor therapy due to the following characters in tumor therapy:Low-cost,diversity of synthesis methods,good biocompatibility and functionalization on the surface of the nanoparticles easily;As good contrast agents for diagnosis of cancer;As a drug carrier for the treatment of cancer.However,the reported cobalt-based nanotheranostic agents still have some disadvantages in tumor suppression such as:The size of the NPs need to make some adjustment to accumulate in tumor highly due to the unreasonable size NPs can be removed from body by reticuloendothelial system?RES?;The specific response in tumor microenvironment needs to be further improved in order to realize the integration of diagnosis and treatment of lesion site.Only these problems are solved,it is possible for the cobalt-based nanotheranostic agents to become applicable in clinical to be as“theranostic agents”or“medicament”.Therefore,the development of“cobalt-based nanotheranostic agent combined diagnosis and treatment”which include some characters like reasonable size and excellent performance in tumor therapy is meaningful.Here,we focused on the preparation for the Co-based nanotheranostic agents and their applications in the tumor therapy.First,formation of hollow manganese oxidant/cobalt oxidant?MCO?NPs can serve as drug-loaded agents such as antitumor drug doxorubicin?Dox?and MCO-Dox can act as good nanotheranostic agents for tumor imaging and tumor therapy.Second,a simple method can synthesize MCO@Au vesicles as a H₂O₂ stimuli nanoagent for imaging-guided chemodynamic and radiate therapy.Third,a method for synthesizing Co Fe₂O₄ vesicles has been developed which can be as better thermal agents for tumor ablation compared with Sn S nanosheets.Fourth,Ni Co₂O₄ synthesized by nano-casting method can serve as good PTT agents for tumor inhibition compared with Sn S NP.The whole point of the dissertation states as following:?1?Synthesis of biodegradable hollow Co-Mn-O nanoparticles?MCO NPs?for tumor therapyTumor is one of the biggest threat to the human health thanks to the tumor microenvironment?TME?is a system of very complex and heterogeneity.Therefore,the study of the nanotheranostic agents of the tumor microenvironment have been paid lot of attention by many scientist.Here,hollow manganese/cobalt oxide nanoparticles?MCO NPs?and antitumor agents such as doxorubicin?DOX?could be encapsulated to the cavity of the hollow MCO NPs?MCO-Dox?through electrostatic interactions.The MCO-Dox can react with GSH,then produce ions of Mn²⁺and Co²⁺for dual T₁/T₂magnetic resonance imaging?MRI?,meanwhile,the released Dox can inhibit the tumor.At last,the MCO-Dox can inhibit the growth of the tumor effectively in vivo.Therefore,the MCO-Dox can be a promising delivery vehicle for imaging and tumor chemotherapy.?2?Synthesis of MCO@Au vesicle as a H₂O₂ stimuli nanoagent for chemodynamic and radiate therapyNanotheranostic agents that are responsive to TME have attracted great attention because they can potentially increase the tumor-to-background ratio of imaging signals,controllable drug release in tumors and even modulate tumor microenvironment for better therapeutic efficacy.Here,we reported good nanotheranostic agents:MCO@Au@PEG-_L-BSO.The formation of the MCO@Au vesicles is through the electrostatic interaction and modified by PEG?MCO@Au@PEG?to improve its biocompatibility,loading _L-buthionine sulfoximine?_L-BSO?as inhibitor of GSH generation?MCO@Au@PEG-_L-BSO?.Chemodynamic therapy?CDT?relies on hydroxyl radical?.OH?to suppress the viability of the tumor after the reaction of H₂O₂ and Mn²⁺which come from degradation of MCO NPs by GSH.In additional,_L-BSO can suppress the generation of GSH in tumor and promote the the amount of the.OH to improve the CDT efficiency.Meantime,Au NPs from the degration of the MCO@Au@PEG-BSO can absorb much more X-ray which can enhance the tumor recession.This study demonstrates that MCO@Au@PEG-BSO can serve as a good nanotheranostic agent of the combination of chemotherapy and radiation therapy for inhabition the tumor growth effectively.?3?Synthesis of Co Fe₂O₄ vesicles as photothermal agents for tumor therapy compared with Sn S nanosheetsVesicles have attracted great attention owing to their high surface area,large hollow volume and diverse hierarchical architectures and morphologies.Here,a universal approach was developed to trigger the assembly of nanoparticles?NPs?and made research for the Co Fe₂O₄ vesicles as photothermal agents for tumor therapy.First,thiol-terminated amphiphilic block copolymers?BCPs?were attached onto Co Fe₂O₄ NPs via a one-step ultraviolet-induced thiol–ene reaction,where the double bond in OA?or/and OAm?of the NPs and thiols in BCPs are coupled into thioether linkage through radical addition.Then NPs-BCPs could be assembled into Co Fe₂O₄ vesicles by film rehydration method.Besides,the results of the Co Fe₂O₄ vesicles study have shown Co Fe₂O₄ vesicles with a good biocompatibility can serve as good PTT agents for suppress the viability of the tumor under the irradiation of the laser compared with Sn S nanosheets and good T₂ MRI contrast agents for tumor imaging.In a word,Co Fe₂O₄ vesicles can serve as good diagnosis and treatment agents for tumor therapy.?4?Synthesis of ordered mesoporous Ni Co₂O₄ as photothermal agents for the tumor therapy compared with Sn S nanoparticlesMesoporous materials which have the characteristics of high specific surface area,regular and orderly pore structure and uniform pore size,can be used as good drug carriers.Therefore,more and more studies on mesoporous materials in tumor are conducted.Here,highly ordered mesoporous Ni Co₂O₄ can be synthesized and serve as a good photothermal agent for tumor therapy.First,ordered mesoporous Ni Co₂O₄and Sn S NP were synthesized.The as-synthesized mesoporous Ni Co₂O₄materials have shown high surface and porous structure.Besides,the results of the MTT test have shown Ni Co₂O₄ as better PTT agents can inhibit tumors compared with Sn S NP.Therefore,Ni Co₂O₄can act as good photothermal agents for tumor therapy and have a potential possibility for carrying anti-tumor drugs.