Construction Of Sulfur Group Nanoplatforms For Tumor Therapy

Cancer has become one of the main killers of human health and life.However,the current conventional cancer therapy?such as surgery,chemotherapy,and radiotherapy?and newly developed micro/noninvasive therapy models?such as PTT,PDT,and CDT?still have some shortcomings.To achieve safer and more effective therapy of tumors,exploring and developing novel nanomaterials for multimodal synergistic treatment has attracted great attention in recent years.In this thesis,basing on the construction of new functional materials,three new strategies were proposed,i.e.,p H-independent CDT to efficiently generate Reactive oxygen species?ROS?,therapeutic-immunomodulatory synergistic therapy of tumors,and photoactivated nanozyme activity for PTT/PCT synergistic therapy of tumors,to address the challenge of tumors therapy.The main research includes the following contents:?1?Cu Fe S₂ NPs for p H-independent chemodynamic and photothermal synergetic tumor therapy.Chemodynamic therapy?CDT?is an emerging field,which utilizes intratumoral iron-mediated Fenton chemistry for cancer therapy.However,the slightly acidic tumor environment is improper for the classical Fenton reaction which is generally energetic at a narrow p H range?e.g.,p H 3?4?.Herein,a kind of ultrasmall bovine serum albumin?BSA?-modified chalcopyrite nanoparticles?BSA-Cu Fe S₂ NPs?was synthesized via a facile aqueous biomineralization strategy,which shows high dispersity and biocompatibility.Interestingly,the obtained BSA-Cu Fe S₂shows a p H-independent Fenton-like reaction,which could exert Fenton-like activity to efficiently generate·OH under weak acidic tumor environment.Combining with the extraordinarily high photothermal conversion?38.8%?,BSA-Cu Fe S₂shows the synergistic function of high photothermal therapy and enhanced chemodynamic therapy,i.e,PTT/CDT.Importantly,such ultrasmall BSA-Cu Fe S₂NPs with around 4.9nm can be quickly clearable out the body through kidneys and liver,thus effectively avoiding long-term toxicity and systemic toxicity.Moreover,BSA-Cu Fe S₂ NPs can be acted as an efficient T₂-weighted MRI contrast agent to guide tumor ablation in vivo.This work offers a universal approach to boost production·OH by a p H-independent Fenton-like reaction strategy and achieves MRI-guided synergistic enhanced photothermal-chemodynamic therapy for high efficient tumor treatment.?2?Therapeutic-immunomodulatory nanoplatform built by in situ synthesis of noncrystalline Selenium in dendritic mesoporous silica nanoparticles.Developing versatile nanomaterials have offered a myriad of opportunities to surmount cancer.Especially,the combining of immunomodulatory effect,enhancing the immune response,into one platform provides a new idea for effective tumor treatment.Herein,for the first time,an in situ growth strategy is developed to construct high dispersed noncrystalline selenium nanoparticles?Se NPs?with thiolated cyclo?Arg-Gly-Asp-Phe-Lys-?mpa???RGD?peptide modification?R-Se@DMSND?for targeted cancer treatment.Se NPs could be homogeneously grown into the pore channels of dendritic mesoporous silica nanoparticles?DMSNs?since the DMSNs could stabilize the Se NPs to prevent their aggregations.Moreover,Se NPs could not only act as a therapeutic agent,inducing ROS overproduction,to effectively suppress primary tumor but also as an immunomodulatory agent to simultaneously inhibit the growth of secondary tumors by enhancement of the immune response,as confirmed by the in vivo results.Such the therapeutic-immunomodulatory strategy of tumorous therapy combining with immunomodulation using one simple nanoplatform may pave a new avenue in the biomedical field.?3?Photo-activated nanoenzyme for tumor synergistic photothermal and photocatalytic chemodynamic therapy.To effectively overcome the problem that traditional PDT and CDT respectively reling on oxygen and acidic conditions,a novel strategy to generate ROS based on photo-activated nanoenzymes is innovatively proposed.We firstly synthesized monodispersed dendritic silica-coated UCNPs composite nanoparticles?UCNPs@DMSNs?through a surfactant-directed self-assembly method.Then the ultra-small Cu S nanoparticles were loaded into the pore channels of UCNPs@DMSNs?Cu S-UCNPs@DMSNs?.Cu S-UCNPs@DMSNs with excellent photothermal performance can be used as PTT agents.Interestingly,under the excitation of 980 nm laser,the UV light generated by UCNPs can further activate the activity of nanozyme to generate free radicals?ROS?by photocatalysis.Moreover,CBS inhibitors,as inhibiting H₂S production,was further loaded into the pore channels of Cu S-UCNPs@DMSNs to suppress tumor growth.This work offers a proof of concept to demonstrate a novel photo-activated nanoenzymes for photocatalytic chemodynamic therapy of tumor.Based on the design and synthesis of nanomaterials,we have constructed three new types of nanomaterials and proposed three new strategies for tumor therapy,such as p H-independent CDT strategy,therapy-immunomodulation strategy,and photoactivated nanozyme activity for tumor synergistic photothermal and photocatalytic chemodynamic therapy.The research in this paper provides a new paradigm for the efficient treatment of tumors.