Mesoporous Polydopamine Coated Gold Nanomaterials And Their Application In Functional Protein Delivery

The development of protein carriers has aroused great attention of researchers in biomedicine.Successful delivery and release of functional proteins highly depend on the protein carriers,which has a decisive impact on the eventual performance.To meet such challenges in the study of protein delivery,a novel nanoplatform on the basis of mesoporous polydopamine(mPDA)was developed in the thesis.Two kinds of organic-inorganic nanohybrids(mPDA coated gold nanoparticles and mPDA coated gold nanorods)were addressed as functional protein carriers to deal with the issues of bioanalysis and cancer tumor therapy.The main research contents of this thesis were introduced as followed.1.Synthesis of core-shell mPDA coated gold nanomaterials and their photothermal conversion property.The organic-inorganic hybrid nanomaterials with mPDA coating were synthesized via a "soft-template" method in a quaternary microemulsion system of water/1,3,5-trimethylbenzene/Pluronic F127/ethane,in a means of spontaneous polymerization of dopamine molecules in a mild alkaline condition.The mesoporous structure(20 nm ca.)could afford enough places for cargo loading.By manipulation of synthesis conditions(reactants ratio,reaction time,and etc.),the morphology and structure of nanomaterials could be controlled accordingly.The results indicated that this polydopamine coating strategy could be virtually applied in various types of inorganic nanomaterials in different size and shape,and the as-prepared hybrids have a satisfactory photothermal conversion efficiency of near-infrared(NIR)light(45.8%).2.Traceable delivery and light-triggered release of recombinant functional protein.The mPDA-coated gold nanoparticles were used as protein nanocarriers,which affords the high loading capacity(473.3±24.9 ?g/mL)in the prescence of nickel ions and phothermal-controlled release(1.0 W/cm2,31.7±1.6%)of recombinant green fluorescent proteins(GFP).Ribonuclease,an intracellular cytotoxic protein,was used as a therapeutic protein model for the proof-of-concept study of controlled protein therapy in vitro and in vivo,addressing the issues of low delivery efficiency of flunctional protein.Plus the strong light scattering and analyzable of gold,this NIR light-triggered protein delivery offered a traceable,non-invasive and remote-controlled scenario for cancer tumor therapy.3.Catechol-modified GFP as a specific biosensor for AI3+.In response to the requirement of a safe and effective Al3+ biosensor,3,4-L-dihydroxyphenylalanine was introduced in the recombinant GFP through residue-specific incorporation.The results demonstrated that the GFP variant could selectively and sensitively detect Al3+ in an enhanced fluorescence mechanism in the range of 1-100 ?M at limit of detection of 1.1?M without inteference from Zn2+.By using the nanocarrier of mPDA coated gold nanoparticles,the biosensor was delivered into the cytosol,which enabled intracellular Al3+ detection.4.Multifunctional photothermal agents for deep-tissue tumor photothermal therapy.mPDA coated gold nanorods were used as a delivery platform for thermal-sensitive papain.The papain-loaded nanomaterials have a high photothermal conversion efficienct(56.5%)and could performed photothermal conversion beneth the tissue cover(7 mm)in the second window of NIR light(NIR-II).Triggered by local temperature increase,the released and activated papain took account for the degradation of extracellular matrix,leading to high accumulation of photothermal agents in tumor site.Therefore,with assistance of deep penetration of NIR-II irradiation,the efficient photothermal conversion was performed in deep tissue,solving the problem of low therapeutic efficiency of deep-tumor therapy.Above all,mesoporous polydopamine coating could integrate multiple modules in one nanoplatform,giving rise to nanocarriers capable of efficient delivery and controllded release of functional proteins.Consequently,this strategy maintained original properties of the inorganic nanoparticle cores and made a full use of mesoporous structure and photothermal conversion of mPDA.The unique surface chemistry of polydopamine further offered optimized modifications of the nanomaterials,which in all providing fundamental guidance for protein delivery research in the future.