Construction Of Multifunctional Gold Nanoparticle-based Nanocarriers And Their Applications In Cancer Therapy

Nanocarrier can prolong the half-life of drug systemic circulation,taking advantage of the inherent enhanced permeability and retention（EPR）effect of tumor vessels,and drugs are able to preferentially accumulate in tumorsite.Multifunctional nanocarriers can combine different functionalities in a single stable construct,such as specific targeting agent with nanoparticles for imaging,cell-penetrating agent,stimulus-sensitive element for drug release,a stabilising polymer to ensure biocompatibility and the therapeutic compound.Multifunctional nanocarriers have emerged as novel bioimaging,diagnostic,and therapeutic agents for the medical reseach.In this thesis,based on the gold nanoparticles,mesoporous silica,zinc oxide quantum dots（ZnO QDs）,copper sulfide nanoparticles（Cu_xS NPs）and antitumor drugs（DOX,PTX）,we have developed two type of gold nanoparticle-based multifunctional platforms for imaging,targeting drug delivery,controlled release of drugs,and combination therapy.This thesis mainly includes the following two aspects:（1）Construction of pH-responsive gold nanoparticle-based nanocarriers and their applications in cancer therapy.The mesoporous silica-coated gold nanoparticles（AuNP@mSiO₂）with a core-shell structure have been successfully fabricated by a facile one-pot process.The ethylene glycol reduction and galvanic replacement reaction can be explotied to prepare gold nanocages with unique and tunable properties.They can be assembled with ZnO QDs,followed by the formation of pH-responsive gold nanoparticle-based nanocarriers.ZnO QDs can not only improve the encapsulation efficiency of drugs but also achieve the control of drug release.These two pH-responsive nanocarriers（AuNP@mSiO₂@DOX-ZnO and AuNC@PTX-ZnO）may be a promising nanoparticles and can be applied for bioimaging,photothermal therapy and chemotherapy.（2）Construction and antitumor application of targeted gold nanoparticle-based nanocarrier.The mesoporous silica-coated gold nanorods（AuNR@mSiO₂）are fabricated by sol-gel method.After the amino functionalization,Cu_xS nanoparticles attach on a AuNR@mSiO₂ surface as a photosensitizer,and folic acid（FA）conjugate with a AuNR@mSiO₂ surface as a cancer cell target.To improve the biocompatiblity and stability of nanomaterial,we modified the nanocarrier with polyethylene glycol（PEG）.Then,achieve the doxorubicin was loaded into the nanoparticles by solvent diffusion and vacuum drying.We have developed the PEG-modified DOX-loaded AuNR@mSiO₂-FA-Cu_xS nanocarriers for combination of photothermal therapy,photodynamic therapy and chemotherapy,and chemotherapy.