Construction And Evaluation For Anti-tumor Propertis Of Mutifunctional Phototherapy Platforms

In recent years,tumors are mainly removed by surgical resection,which is one of the most common therapeutic method for cancer treatment.However,surgical resection often results in side effects such as large wound area and damage to normal tissues.In addition,radiotherapy and chemotherapy are often introduced as adjuvant treatment after surgery,which can also cause serious side effects to human body.Therefore,it is very important to find suitable methods for tumor ablation and improve the survival rate of patients.So far,many new cancer therapeutic strategies have been adopted,such as phototherapy,chemodynamic therapy,gene therapy,etc.Among these methods,non-invasive phototherapy including photothermal therapy（PTT）and photodynamic therapy（PDT）has received widely attention.Based on the above reasons,a series of multifunctional phototherapy platforms were designed in this thesis,and their anti-tumor properties were also studied in vitro and in vivo.First of all,to solve the diploma that the tumor isn’t completely removed by surgery resulting in the recurrence of cancer,a multifunctional hydrogel was designed for postoperative filling of the wound and PTT combined with PDT for residual tumor.The hydrogel was based on Gellan Gum cross-linking by Ca²⁺and used to load photothermal agent gold nanorod（AuNR）and photodynamic agent methylene blue（MB）.Then,its morphology,mechanical properties,drug release,photothermal and photodynamic properties were characterized.The results showed that this hydrogel possessed good injectable ability,photothermal and photodynamic properties,controllable mechanical properties,superior stability and the ability of prevention of the rapid loss of nanomaterials.It also showed good cytocompatibility and inhibition effect of cancer cells in vitro.Then,to solve the problem that some nanomaterials are unable to self-degrade when applied in vivo and may cause biotoxicity,and to overcome the unsatisfactory therapeutic effects caused by monotherapy,a nanoplatform of biodegradable antimonene nanosheets（AMNSs）coated by natural macromoleculechitosan（CS）and used to load gold nanoparticles（AuNPs）with clearable small sizes and photosensitizer IR820 was designed and prepared for combined phototherapy and cell imaging.And its morphology,biodegradablity,photothermal and photodynamic properties were measured.Meanwhile,the anti-tumor and fluorescence imaging property were detected via cell experiment.The nanoplatform has demonstrated to contain satisfying biodegradability,good photoacoustic imaging performance,excellent photothermal and photodynamic properties,as well as excellent combined therapeutic efficacy and fluorescence imaging function in vitro cell experiments.Finally,many nanomaterials often show short blood half-life and poor tumor accumulation,which results in unsatisfactory therapeutic effect.To solve this problem,a multifunctional peptide coating mainly composed of mitochondria-targeted segment,Cathepsin B-responsive segment and zwitterionic antifouling segment from the inside out was designed and prepared.Then gold nanorods were modified with the peptide via ligand exchange and obtained a nanoplatform based on mitochondria-targeting and the responsiveness of Cathepsin B for PTT.The morphology,UV-Vis absorption spectra,potential,stability and photothermal properties of the nanoplatform before and after the enzyme response were studied.In addition,the targeting and anti-tumor properties of the nanomaterial was investigated at the cellular level,and the tumor ablation ability of the nanomaterial in vivo was investigated in mice.This nanoplatform displayed good photothermal property,stability and enzyme responsiveness,and possessed good biocompatibility,satisfactory mitochondria-targeted ability,leading to effective subcellular hyperthermia treatment and excellent ablative ability of tumor.