Design And Fabrication Of Nanomaterials Based On Polypeptide/Peptide For Tumor Theranostic Applications

As a major killer of human health,the effective prevention and treatment of cancer has become a top priority in scientific research.For a long time,scientists were strived to seek safe and useful strategy for tumor diagnosis and treatment.Traditional small molecule anti-tumor drugs,because of poor water solubility,easy to be rapidly degraded,non-specific distribution in vivo and other disadvantages,the clinical efficacy was severely limited.Therefore,the intelligent nano-drug delivery system that can overcome the complex physiological barrier in the body has attracted great attention.In this thesis,based on the transmission mechanism of nano-system and the special physiological environment of tumor,we designed and fabricated a series of physiological signal stimulus-response nano-transmission systems,for achieving targeted therapy and Real-time diagnosis in the tumor region.The detail is displayed as follow:In chapter one,the characteristics of tumor micro-environment and its application in tumor targeting were introduced.Moreover,the strategy of designing multifunctional intelligent nano-delivery system with stimulation response and its research progress in tumor diagnosis and treatment were also introduced.In chapter two,in view of the complexities of the tumor micro-environments,multicolored polypeptide nanoparticles were developed as fluorescent probes,through hydrogen bondings and hydrophobic interactions between two amphiphilic polypeptides.By incorporating the thermos-and p H-sensitive units into the amphiphilic polypeptides,double stimulus responsive micelle was obtained.Moreover,fluorescent micelles were achieved by the incorporation of two types of flurophores with different colors into the nanoparticles.It was found that the fluorescence-labeled micelles exhibit thermos-and p H-depedent fluorescence,indicating that these micelles might find wide applications in probing in complicated microenviroments.In chapter three,a novel peptide micelle system with p H-responsibility for gene and drug release was designed and fabricated,through the host-guest interaction between α-Cyclodextrin(α-CD)and phenyl groups as well as β-Cyclodextrin(β-CD)and Adamantane(Ad).Drug release behavior of the peptide pro-drug system and the in vitro cell inhibition were studied,the results suggested that the peptide nanocarrier exhibited a much faster drug and gene release rate in endosome that in normal physiological environment,which led to effective synergetic anti-cancer effects in cancer cells.In chapter four,a novel type of multistage tumor-triggered targeting delivery system based on gold nanoparticles(Au NPs)was designed for the diagnosis,treatment and real-time monitoring of anti-tumor.β-CD was conjugated to the surface of Au NPs,then chromophores and drugs were introduced onto the surface of the Au NPs via host-guest interaction between β-CD and Ad through different environmentally sensitive groups.Because of the energy resonance effect on the surface of Au NPs,the system was in the state of fluorescence quenching under physiological conditions.After reaching the tumor site,the chromophores or drugs loaded on the nanotemplate was released from the surface of Au NPs under different conditions,and the fluorescence was rapidly restored to the excited state.Therefore,tumor diagnosis,targeted therapy and real-time apoptosis imaging could be performed simultaneously.