Tumor Theranostics On The Basis Of Polymeric Nanocomposites

Because of its high metastasis,high recurrence,and low prognosis,cancer is difficult to completely eradicate by conventional methods such as surgery and chemotherapy.It has become the second most common cause of death after cardiovascular and cerebrovascular diseases in the world.Hence,it is urgent to develop novel methods for treating tumors.Due to the limitations of conventional treatment methods,nanomaterials with unique physical and chemical properties have shown great potential for the development in the biomedical field.Therefore,the use of nano-materials to construct multifunctional tumor diagnosis and treatment reagents,namely medical theranostics reagents,such as magnetic resonance imaging,photothermal therapy,chemotherapy,and immunotherapy,have attracted more and more attention.In this article,we use nano-materials to construct multifunctional noninvasive tumor theranostics reagents to achieve both in-situ diagnosis and elimination of primary tumors while also fighting and preventing the occurrence of metastases.In the second chapter,we constructed a copper-loaded polydopamine nanosphere with dual pH/near-infrared response for multimodal tumor diagnosis and therapy.Polydopamine nanospheres have good biocompatibility,metabolism and many other advantages.However,compared with other composites,single dopamine nanospheres have relatively low photothermal conversion efficiency and molar extinction coefficient,and can only be used as a single photothermal therapy agent and other shortcomings.To solve this problem,we introduced elemental copper which is necessary for the human body during the polymerization process.The dopamine nanospheres complexed with copper not only improve its photothermal properties,but also can be used as T₁ contrast agents for magnetic resonance imaging.The difference in the pH environment between the tumor area and normal blood vessels makes it possible for our nanoparticles to release relatively high amounts of Cu²⁺only in the tumor area,which thus has a certain degree of chemotherapy effect on the tumor.Above all,we have built a multifunctional theranostics nanodevices for magnetic resonance imaging-guided thermochemotherapy with minimal side effects.In the third chapter,we synthesized polydopamine-capped Fe₃O₄ superparticles based on the strong adhesion of dopamine.Superparamagnetic Fe₃O₄ nanoparticles are a kind of widely used magnetic resonance imaging T₂ contrast agent.However,because of its low molar extinction coefficient,Fe₃O₄ can only provide magnetism and is used as a contrast agent in current literature reports.In our experiments,we found that the assembly of Fe₃O₄ nanoparticles into superparticles by self-assembly can significantly improve their photothermal performance and magnetic imaging capabilities,making it possible to obtain significant theranostics effect in a small amount.However,in the process of assembling superparticles,we inevitably introduced surfactants.In order to reduce its toxicity and improve biocompatibility,we modified polydopamine shell on its surface.Based on the above ideas,we have constructed polydopamine-capped Fe₃O₄ superparticles theranostics reagent for magnetic resonance imaging and photothermal therapy of tumors.In the fourth chapter,we constructed photothermal-activatable Fe₃O₄ superparticles nano-drug carriers combined with PD-L1 immune checkpoint blockade therapy for anti-metastatic cancer immunotherapy.In the previous chapter,polydopamine-capped magnetic superparticles still had some drawbacks,such as the introduction of toxic surfactants and the inability to act as drug carriers for drug loading.In this chapter,we used poly（ethylene glycol）-blocked poly（lactide-co-glycolic acid）amphiphilic copolymers instead of surfactants to synthesize biocompatible Fe₃O₄ superparticles in one step.The characteristics of the thermosensitivity of copolymer achieve the purpose of local release of immune drugs,thereby causing the body’s immune response.Further combined with PD-L1 immune checkpoint blockade therapy,in situ elimination of tumors,while preventing its transfer to the lungs/liver and inhibit the growth of pre-existing distant tumor without laser irradiation treatment.