Polydopamine-coated Pt@mesoporous Au Nanocomposites For Tumor Therapy

In recent years,with the continuous development of nanotechnology.Multifunctional nanocomposites have been widely used in the field of tumor therapy.Due to the heterogeneity,complexity and diversity of tumors,it is difficult for a single tumor treatment method to achieve an ideal therapeutic effect.Therefore,combining multiple treatment modalities to achieve synergistic treatment of tumors has become a research hotspot.In this context,we designed a novel nanotherapeutic platform.The surface of Pt@mesoporous Au nanomaterials was coated with polydopamine(PDA)shell,and doxorubicin(DOX)was loaded in the PDA shell,and GOx and NH2-PEG5K-c RGD were loaded on the surface of the PDA shell.NH₂-PEG_5K-c RGD can specifically bind to the?v?₃integrin overexpressed in tumor cells,which enriches the nanomaterials in the tumor area.GOx can react with glucose in tumor cells to generate gluconic acid and H₂O₂for starvation treatment.Pt can catalyze the decomposition of H₂O₂in tumor cells to generate O₂,relieve tumor hypoxic microenvironment and promote the effect of starvation therapy.Taking advantage of the excellent photothermal properties of mesoporous Au and PDA,nanomaterials can be used for photothermal therapy.DOX can damage the DNA of tumor cells and is used in chemotherapy.Finally,the ability of chemotherapy-photothermal therapy-self-promoting starvation therapy to synergistically treat tumors is realized.In chapter 2,we performed a series of characterizations on Pt@Au@PDA-DOX-GOx-c RGD to demonstrate the successful preparation and excellent physicochemical properties of the nanomaterials.The size of the prepared nanoparticles is 106nm,the thickness of the PDA shell is 15 nm,and the Pt@Au is a cubic crystal phase.The photothermal conversion efficiency of the nanoparticles can reach 52.45%,and the photothermal stability is good.The loading of DOX is 44.06%,and the loading of GOx is 12.79%.Subsequently,we performed cellular experiments to demonstrate that the nanomaterials could be efficiently taken up by MCF-7 cells.The excellent antitumor ability of nanomaterials was demonstrated by testing cytotoxicity,AM/PI live and dead cell staining,apoptosis and ELISA.In chapter 3,we explored the antitumor effect of nanomaterials by constructing animal models.The experimental results show that nanomaterials can be enriched in the tumor tissue area and effectively inhibit tumor growth.After the treatment,the tissue sections and blood biochemical indexes of the mice in the treatment group were compared with those of the mice in the control group.We found that the treatment process had less effect on the mice,demonstrating the high biosafety of the nanomaterials.In summary,our designed Pt@Au@PDA-DOX-GOx-c RGD nanotherapeutic platform exhibited excellent antitumor effects in both in vitro and in vivo experiments.Realization of chemotherapy-photothermal therapy-self-promoting starvation therapy synergistic therapy for malignant tumors.