| Photodynamic Therapy?PDT?has been attracted widely attention as a novel treatment of cancer,which has the advantages of minimally invasive,non-resistance,and local treatment.Moreover,the cost of PDT is low,which makes it have great development prospects.However,PDT also has some serious shortcomings,such as short treatment depth,skin phototoxicity,and treatment effects that depend on concentration of intracellular oxygen,which limit the clinical application of PDT.For the problems of shallow light penetration depth of PDT,poor tumor targeting and skin phototoxicity,the first part of this study designed and prepared a tumor-specific targeted up-conversion nanoplatform modified by photosensitizers of PDT and chemotherapy drugs?UCNP@SiO2/PPa&DOX@Cs-FA?.The layer of mesoporous silica coated a homogeneous core-shell structure with up-conversion nanomaterials NaGdF4:Yb,Er@NaGd F4:Yb,Nd excited by near-infrared light,which modified with the excellent photosensitizer PPa absorbed both green and red light and the classic chemotherapeutic drug doxorubicin?DOX?in the pores of the SiO2 layer.Finally,the folate-coupled chitosan?Cs-FA?was modified on the surface of the SiO2layer to obtain targeted and biocompatible UCNP@SiO2/PPa&DOX@Cs-FA nanoplatform.It has a very high efficiency of fluorescence emission resonance energy transfer.The singlet oxygen?1O2?yield in vitro is 79.1%,which is far greater than that of free PPa?27.6%?.The ability of anti-photobleaching is strong.The covalent conjugation between PPa and nanomaterials ensured stable delivery in vivo.DOX was physically adsorbed and encapsulated in the channel.The slowly release of slightly acidic?pH 5.2?and stimulus respond of GSH was the best effect?The amount of DOX release was 84%at 16 h?,proved that the obtained nanoplatform UCNP@SiO2/PPa&DOX@Cs-FA was responsive to stimuli of tumor microenvironment.UCNP@SiO2/PPa&DOX@Cs-FA had good behavior of cell uptake,could generate enough 1O2 in the cell,and had function of fluorescence imaging.The PDT activities in vitro experiments demonstrated that the rate of tumor growth inhibition was concentration-dependent,and the combined effect of PDT and DOX was better than that of PDT alone or DOX alone.The morphological changes of Hela cells before and after PDT treatment were consistent with PDT activity experiments,which displayed that UCNP@SiO2/PPa&DOC@Cs-FA nanoplatform was triggered by 808 nm laser,and the anti-cancer efficiency of PDT combined with DOX was significantly enhanced.In order to solve the problems of hydrophobicity and skin phototoxicity of PDT drugs,its need for the good stimulus response drug-controlled release system.In the second part of this study,a pH-sensitive graphene oxide conjugated rhodocyanin-18 methyl ester?Pu18?nanocomposite was designed and synthesized.The GO-Pu18 nanomaterial was obtained by simple ultrasonic and stirring.The obtained GO-Pu18 nanomaterial had a longer absorption wavelength?751 nm?,that made it more suitable for the treatment of deeper tumor tissues.Compared with free Pu18,GO-Pu18 showed significant fluorescence quenching,greatly reducing skin phototoxicity.It exhibited pH-sensitive drug release behavior.Pu18 was more easily released from the GO-Pu18 complex in weak acid environment than in neutral environment,which indicated that GO-Pu18 can be used in tumor treatment due to its weak acid environment surrounding tumor tissue.The 1O2yield???=62.60%?and the photostability of GO-Pu18 was good.GO-Pu18 exhibited excellent cytotoxicity and negligible dark toxicity in in vitro anticancer activity experiments.Type I and type II photodynamic reactions occured simultaneously in HepG-2 cells,and type II played a dominant role.The cellular uptake of GO-Pu18 was faster than that of free Pu18,and it rapidly released Pu18 in cell.At the same time,nanomaterials have the function of fluorescence imaging. |
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