Development And Application Of Mesoporous Polydopamine PH Response Drug Loading Platform And Fluorescent Polydopamine Probe

With the development of nanotechnology,polymeric nanomaterials have become a widely used emerging material.Nanomaterials have a variety of advantages such as simple structure,easy modification and good biocompatibility.Therefore,it has become an important part of medical field and can be used in drug transportation,monitoring and treatment progress,early diagnosis of diseases and wound healing etc.Polydopamine（PDA）nanomaterials,as a new type of nanomaterial,have many characteristics such as higher photothermal conversion performance,great adhesion,easy modification,chelating metal ions,richπelectrons,great water solubility and biocompatibility.Hence,PDA has excellent application potential in drug transportation and biological testing.At present,there are many troubles in the design and synthesis process of PDA nanomaterials such as complex design,long synthesis time,and cumbersome synthesis.PDA,a nanoplatform,must possess drug loading ability,drug release ability,and lysosomal escape ability in numerous research.At the same time,drug resistance is also a tough barrier to kill cancer cells.Therefore,it is necessary to develop a PDA-loading platform with high loading drugs,specific release drugs,lysosomal escape and regulating drug resistance.PDA as a fluorescent nanoprobe can be used for the detection of cancer-related markers,and it is particularly important to improve its stability,sensitivity and specificity.Therefore,it is necessary to construct fluorescent PDA（FPDA）nanoprobes to achieve stable,sensitive and specific detection of cancer markers.In summary,the main content of this thesis was divided into two aspects according to the characteristics of the PDA.（1）A p H response nanoplatform was built based on mesoporous polydopamine（MPDA）nanoparticles for loading chemotherapy drugs.Glucosylceramide synthase（GCS）suppression play a key role in improving drug resistance when chemotherapy drugs act on cancer cells.First of all,MPDA is synthesized and N,N-dimethyl-1,2-ethanediamine（DMEA）was used to modify MPDA surface for improving lysosomal escape ability.Chemotherapeutic drugs are adsorbed to the MPDA surface throughπ-πaccumulation interactions and hydrophobic interactions.Finally,in order to achieve p H response release and avoid early penetration of DOX,calcium phosphate（Ca₃（PO₄）₂,Ca P）was wrapped on the outer layer of MPDA,obtaining the nano-load drug platform MPDA-DMEA-Ca P（DOX）.The results showed that when MPDA-DMEA-Ca P（DOX）combined with GCS inhibitor acted on cells,GCS inhibitor could reduce the drug resistance of cancer cells to DOX and improve the therapeutic effect of DOX.（2）A low-aggregation PDA fluorescent nanoprobe is constructed,which achieves fast,sensitive and selective detection of vitamin B₁₂(VB₁₂)and Al³⁺by the"Off-On"detection strategy.First,the dopamine（DA）was oxidized under alkaline conditions and the FPDA was synthesized by controlling the aggregation time.Then.VB₁₂ and Al³⁺can be detected by FPDA.The concentration of VB₁₂ is related to FPDA’s fluorescent intensity linearly（R²=0.996）,and the limit of detection（LOD）is 1.954μM in the range of 20-220μM.In the range of 2-18μM,the concentration of Al³⁺is linearly related to the fluorescent intensity of FPDA（R²=0.99）,and the LOD is 0.114μM.Moreover,FPDA only response specially to Al³⁺compared with common metal ions,amino acids,and reduction substances.