Fabrication of Theranostic Platform Based on Cationic Polymers and Iron Oxide/gold Nanoparticles
Author:Wang Ran Ran
Supervisor:zhao na na xu fu jian
Cancer is one of the most disastrous diseases worldwide.Various treatment modalities are employed for cancer therapy.Gene therapy is a promising way for curing cancer at the molecular level.It is crucial to fabricate efficient and safe gene vectors for efficient gene therapy.Cationic polymers with the characteristics of large scale production and low immunogenicity is common non-viral gene vectors.Photothermal therapy utilizes the heat generated by the photothermal conversion agents to kill cancer cells exhibiting the advantages of non-destruction,non-toxicity,targeting,and high-efficiency.Inorganic nanoparticles with near-infrared absorption are generally used as photothermal therapeutic agents.Chemotherapy is an effective treatment modality using drugs to inhibit the development of cancer without limited penetration depth.Real-time imaging of tumors during theatment can effectively monitor changes of the disease position and guide the subsequent therapeutic processes,which is important to enhance the effectiveness.The design of cancer theranostic platform adoptting organic/inorganic composite nanoparticles can combine the excellent optical,and magnetic properties of inorganic nanoparticles with biocompatible organic materials realize complementary imaging guided tumors treatment.Since the morphology,size and surface properties of organic/inorganic composite nanoparticles affect their biological behaviors,we use a low-toxicity cationic polymer and inorganic nanoparticles which endowing unique physicochemical properties,such as gold,iron oxide and silica,to construct multi-functional tumor theranostic platforms with special morphology.One-dimensional magnetic nanostructures exhibit excellent magnetic properties and can promote endocytosis.The combination of one-dimensional magnetic nanostructures and cationic gene vectors will obtain superior gene delivery efficency."Graftting from" strategy was employed to construct one-dimensional peapod-like organic/inorganic composite nanoparticles.Firstly,one-dimensional peapod-like magnetic nanoparticles(p-Fe3O4@SiO2,p-FS)were synthesized successfully without template or magnetic field.The multi-functional tumor diagnosis and treatment platform(p-FS-PGEA)was then constructed by the grafting of ethanolamine(EA)-opened glycidyl methacrylate(PGEA)via atom transfer radical polymerization(ATRP)and used for gene delivery.The experimental results show that compared with the ordinary spherical composite nanoparticles,peapod-like composite nanoparticles can significantly improve gene transfection efficiency.The presence of an external magnetic field can further increase gene transfection efficiency.In addition,the peapod-like composite nanoparticles can combine the magnetic properties of p-FS to achieve non-invasive magnetic resonance imaging(MRI)guided therapy.Better therapeutic effects can be achieved by designing the composition and morphology of organic/inorganic composites for combination therapy.Firstly,caplike gold and hollow star-shaped silica were integrated in an inorganic nanostructure(starlike Au@SiO2)through the sacrificial template method.PGEA was grafted onto the surface of starlike Au@Si02 controllablly to fabricate a multi-functional diagnostic and therapeutic platform.We found that caplike gold nanoparticles with a cross cavity possess photothermal effect thus can be used for photothermal therapy.The internal cavity of silica nanoparticles endow them drug loading capability.The loaded drug could be used for chemotherapy.The cationic polymer PGEA grafted from the inorganic surface possesses good gene transfection properties and could be used for gene therapy.In addition,the plasmon resonance characteristics of caplike gold nanoparticles in the near-infrared region guarantee the ability of photoacoustic imaging and CT imaging.The experimental results show that compared with ordinary spherical organic/inorganic composite nanoparticles,the starlike structure with sharp corners facilitate endocytosis,which contributes to enhanced anti-tumor effect.The organic-inorganic composite nanostructure combined gene therapy,photothermal therapy,chemotherapy,CT and photoacoustic imaging in one system realizing dual imaging guided multimodal therapy.Self-assembly as a promising method for materials construction can organize several nanoparticles into one specific assembly nanostructure.The assemblies may achieve new or superior properties compared to their individual counterparts.Firstly,magnetic nanoparticles which can be used for magnetic targeting and MRI were chosen to synthesize bowl-shaped and spherical magnetic assemblies(b-MNPs and s-MNPs)controllably through typical emulsion method.The surface of magnetic nanoparticles(MNP)was readily functionalized with host-guest assembly of adamantine(Ad)and CD-PGEA to fabricate multi-functional theranostic platform(MNP-PGEA).Cationic polymer PGEA can be used for gene therapy.Iron oxides with photothermal properties are expected to be used for photothermal therapy.Compared with conventional spherical composite nanoassembly,the bowl-shaped assembly is more conducive to endocytosis,which may produce enhanced anti-tumor effect.The utilization of MRI and magnetic targeting function of assemblies can acheive enhanced imaging guided therapy.In summary,we successfully fabricated organic/inorganic hybrid nanoparticles with excellent optical,magnetic properties,and special morphology for the construction of a multifunctional cancer theranostic platform.The superior morphology of the organic/inorganic hybrid nanoparticles resulted in higher endocytosis efficiency.Cationic polymers were used for efficient gene delivery.The inorganic components of iron oxide,hollow starlike silica oxide and caplike gold nanoparticles was applied for magnetic field-enhanced gene transfection and MRI;effective chemotherapy;photothermal therapy,CT,and photoacoustic imaging respectively.The multi-functional theranostic platforms based on organic/inorganic hybrid nanoparticles realized effetive imaging-guided therapy.These materials are of great significance for the design of advanced multi-functional theranostic platforms for cancer therapy.