Emulsion Based Assembly Of Block Copolymer Tethered Gold Nanoparticles And Applications In Theranostic

With the development of nanoscience and nanotechnology,more and more studies prove that the assemblies of inorganic nanoparticles with specific structure show fantastic optical,electrical,or magnetic characteristics which are significantly different from dispersed single nanoparticles before assembly,and are widely used in tumor diagnosis and therapy.However,due to the limit of morphologies,it is still challenging to obtain anisotropic assembly materials of inorganic nanoparticles in the solution state,which seriously hinders the further study of the collective properties of the assemblies and the expansion of biological applications.Therefore,it is desirable to organize assemblies with different structures.Based on this,nanoparticles were modified with structure-guided amphiphilic block copolymers to prepare nanohybrids for assembly,and the anisotropic assembled structure were constructed under emulsion-confined conditions.The amphiphilic block copolymer-modified nanohybrids has the function of surfactants,which can significantly reduce the interface tension of the oil-water interface.The nanohybrids tend to be anchored at the emulsion interface,and limited within the emulsion droplets.Moreover,we introduced another surface-active substance,interfacial competitive adsorbents,to compete with the block copolymer grafted gold nanoparticles on the interface,and control the assembly behavior of gold nanoparticles.The morphology of assemblies can be regulated by interfacial competitive adsorption accurately.Initially,we studied the unary assembly of PDM-PMMA-SH modified gold nanoparticles(Au@BCP).The adsorption of Au@BCP on the oil-water interface can be regulated by controlling the concentration of Au@BCP and surfactants to obtain various assembly structures.Further,we regulated the competitive adsorption of PDM-PMMA-SH-modified gold nanoparticles(Au@BCP)and biodegradable free polymer(PLGA)on the emulsion interface to prepare A PLGA-Au binary assembly with flexible gold assembly patterns.The PLGA-Au binary assembly with various patterns(J-PLGA-Au,R-PLGA-Au,V-PLGA-Au)such as one-dimensional assembly arc,assembly ball crown,two-dimensional assembly disk,and assembly ring can be obtained by adjusting the concentration of Au@BCP,surfactant,and PLGA,or the type of surfactant.Since the R-PLGA-Au assembly(RPA)with a gold assembly ring pattern has a stronger photothermal conversion efficiency than unassembled Au@BCP,we studied the biological applications of RPA.RPA has an excellent performance in drug controlling release,photoacoustic imaging,and chemo/photothermal synergistic therapy.As expected,RPA demonstrated outstanding photothermal performances compared with discrete gold nanoparticles.It is also interesting to find that RPA underwent fusion and regrowth under NIR laser irradiation.After the process of secondary assembly,the resultant larger particles could favor longer residence time in tumors to monitor the therapeutic processes.Moreover,the PLGA segment of RPA was investigated for drug loading and NIR-triggered release,which showed potential of PAI-guided responsive PTT/chemotherapy.In addition,we systematically studied the mechanism and influencing factors of the emulsion system.The competition among gold nanoparticles,PLGA and surfactants is considered to play a pivotal role during the self-assembly process.The feasibility of the remote activation of PAI-guided complementary PTT/chemotherapy with prolonged residence time was also validated in vivo.Finally,in order to further confirm the rationality of the "Interfacial Competitive Adsorption Theory",we replaced free polymers(PLGA)with inorganic nanoparticles(Fe3O4 and Cu2-xS)as "Interfacial Competitive Adsorbents",and co-assembled with amphiphilic block copolymer modified gold nanoparticles(Au@BCP)to prepare Au-Fe3O4 and Au-Cu2-xS binary assemblies.It is worth mentioning that regardless of whether the"Interfacial Competitive Adsorbent" is a free polymer(PLGA)or oil-phase nanoparticles(Fe3O4 and Cu2-xS),Au@BCP can be organized into similar Au@BCP assembly patterns(ring R-PLGA-Au in Chapter 3 and ring R-Au-Fe3O4 in Chapter 4)via regulating the concentration of Au@BCP,interfacial competitive adsorbents,and the surfactants.We have initially demonstrated that the morphology of a binary assembly is regulated by two factors,interfacial competitive adsorption and the structure of emulsion.This proves once again that the assembly pattern of the block copolymer modified nanoparticles in the binary assemblies is less affected by the size or morphology of the element,but mainly depends on the positioning of the elements on the oil-water interface.This concept of "Interfacial Competitive Adsorption" provides theoretical guidance for us to construct hybrid structures with multi-elements of different morphologies,and lays the foundation for the study of the structure-activity relationship between dispersed nanoparticle and assemblies,which is potential for accurate imaging and efficient therapy.