Fabrication Of Multifunctional Polymer-Inorganic Nanomaterials For Cancer Theranostics

The rapid development of nanoscience and nanotechnology has greatly promoted the widely application of nanomaterials in the biology and medicine fields.Recently,polymer-based photothermal nanomaterials have drawn much attention in the biomedical field owing to their excellent biocompatibility,functional groups on the surface,strong near-infrared?NIR?absorbance,high photothermal conversion efficiency and outstanding photostability,which are far superior to conventional inorganic photothermal agents such as gold nanorods?GNRs?and copper sulfides used in photothermal therapy of tumors.In addition,polymer-based photothermal agent is used as a host material,combined with various functional guest nanomaterials such as gold nanoparticles?NPs?,mesoporous inorganic NPs,magnetic NPs,and fluorescent molecules as the guest materials,to construct a multifunctional inorganic-polymernanocompositeforimaging-guidedsynergisticcancer chemo-phototherapy in vivo.This thesis synthesized multifunctional polymer-based NPs and explored its role in potential applications of cancer treatment such as drug delivery,controlled drug release,bioimaging and so on.The specific research content is as follows:?1?Firstly,a simple and facile strategy to prepare well-dispersed eccentric polypyrrole@?acrylic acid?NPs?PPY@PAA NPs?is developed,in which PAA as a nanoreactor due to the strong water absorption of PAA molecules,followed by growing small fluorescent silica NPs?fSiO₂ NPs?inside the PAA networks,resulting in the formation of eccentric PPY@PAA/fluorescent mesoporous silica?PPY@PAA/fmSiO₂?core-shell NPs.The obtained eccentric PPY@PAA@fmSiO₂core-shell NPs possess an excellent drug loading capability,strong NIR absorption and fluorescence intensity.Besides,DOX release from the DOX-loaded PPY@PAA/fmSiO₂ NPs can be controlled under pH/NIR conditions.Finally,the anticancer potentials of the PPY@PAA@fmSiO₂ core-shell are tested in vitro and in vivo,so as to effectively treat cancer.?2?This paper presents for the first time a facile,novel yet reproducible synthetic strategy for the synthesis of well-dispersed polydopamine/poly?acrylic acid?Janus NPs?PDA/PAA JNPs?under mild conditions,which can be further employed as templates to selectively grow mesoporous calcium phosphate?mCaP?on the surface of PAA domains.The PAA can be removed by washing with water to generate the unique PDA/mCaP H-JNPs with dual distinguished domains for further applications.In the obtained PDA/m CaP H-JNPs,the exposed PDA domains were selectively functionalized with indocyanine green?ICG?and methoxy-poly?ethylene glycol?thiol?PEG-SH?to achieve near-infrared?NIR?absorbance,superior photoacoustic?PA?imaging capability and biocompatibility as well as long circulation time,and the hollow cavities and CaP domains with mesoporous structure served as a storage space and passage for the anti-cancer drug of doxorubicin?DOX?.The resultant PEG-ICG-PDA/mCaP H-JNPs were employed as a new theranostic agent for PA imaging-guidedsynergisticchemo-photothermalcancertherapy.Through the implementation of this dissertation,the novel synthetic strategy for precisely preparing the multifunctional PDA/mesoporous inorganic substances hollow Janus nanocomposites can be established,which provides the new idea to synthesize polymer-inorganic Janus nanomaterials with unique shape and structure and further promotes the application of Janus NPs in cancer theranostics.?3?A facile and novel synthetic strategy for the synthesis of monodispersed gold nanorod-poly?acrylic acid??GNRs-PAA?Janus NPs was proposed.Then the PDA was selectively anisotropically grown on the PAA template to form the unique monstera flower-like GNR/polydopamine bowl?GNR/PDA bowl?with a spadix-bract nanostructure.The obtained monstera flower-like GNR/PDA bowl spadix-bract NPs are preferentially decorated with 1-dodecanethiol?DT?on GNR domains?spadix?,which can serve as a storage space and passage for the hydrophobic anti-cancer drug of 10-hydroxycamptothecine?HCPT?.Meanwhile the surface of PDA bowl?bract?can load hydrophilic anti-cancer drug of doxorubicin?DOX?.The resultant DT-GNR/PDA bowl spadix-bract NPs were used as imaging contrast agents for dual-mode bio-imaging?PA and computed tomography imaging?in vivo.Drug-loaded nanocarriers can achieve controlled drug release when the pH value changes to acidic.At the same time,since GNRs and PDA possess NIR absorbance,diffusion of drug molecules can be promoted by NIR laser irradiation,thereby achieving dual-responsive controlled drug release.Finally,the effect of the multi-drug synergistic chemo-photothermal therapeutic agent in vivo to kill the tumor was examined,achieving 100%of tumor ablation.Through the exploration of this paper,the synthetic approach could be extended to prepare inorganic/PDA bowl NPs for co-delivery of different anticancer drugs and multimodal imaging.We envision this discovery of the unusual monstera flower-like DT-GNR/PDA bowl spadix-bract NPs may lead to further development of new concepts and architectures of nanocarriers,thus allowing for more opportunities in multi-drug delivery and combined therapy.