Preparation,Characterization Of D-?-A-based Nanophotosensitizcr And Its Application In Tumor Photothcrapy

Phototherapy attracts considerable attention as novel cancer treatment,including photothermal therapy(PTT)and photodynamic therapy(PDT).The mechanism of phototherapy is that,tumor cells are damaged by local heat and reactive oxygen species(ROS)generated from photosensitizers under irradiation.Therefore,phototherapy exhibits several advantages,including low toxicity,good targeting,low invasiveness.Photosensitizers,light and in vivo oxygen are three essential elements of phototherapy.And photosensitizer is the key component.According to the structure of photosensitizers,it can be divided into(1)porphyrins,such as hematoporphyrin,photofrin,etc.;(2)Chlorophyll,such as chlorin,purpurin,etc.;(3)dyes,such as phthalocyanine,boron-dipyrromethene and so on.Generally,traditional photosensitizers have the problems of poor water solubility,poor photostability,limited near-infrared absorption,low photothermal conversion efficiency or poor tumor targeting.Therefore,the design of new photosensitizers to overcome these problems is important for tumor precise treatment.In this thesis,a near-infrared nonlinear organic chromophore molecule(NOC)was utilized as a potential photosensitizer with unique photoconversion ability.Firstly,the amphiphilic copolymer PEG114-b-PCL60 was used to fabricate NOC-loaded nanoparticles(NOC-NPs).Upon irradiation,excited NOC-NPs were able to undergo intrinsic intramolecular charge transfer(ICT)channel to generate both abundant singlet oxygen and local hyperthermia,thus affording synergistic photodynamic therapy and photothermal therapy for tumor ablation.This thesis will include the following contents:Chapter 1:The current situations of tumor therapy and phototherapy were firstly introduced.The phototherapeutic mechanism,development and applications of photosensitizers are also described.According to the research background,the basis of this thesis is clarified.Chapter 2:The perparation and characterization of NOC-NPs were studied in details,including UV-vis absorption,fluorescence emission,the ability of ROS generation,photothermal conversion efficiency and photostability.The results show that,NOC-NPs had an average diameter of 66.6� 0.8 nm,and strong absorption peak at 720 nm.NOC-NPs showed a superior ability to generate local heat(??36.1%)and abundant singlet oxygen(???0.29)through nonradiative trasition upon irradiation.In addition,NOC-NPs had a strong capacity to resist photobleaching.Chapter 3:The in vitro biological effects of NOC-NPs were investigated,including cellular uptake,subcellular distribution,ROS generation and photo-induced intracellular translocation.The cytotoxicity of NOC-NPs and influence to DNA synthesis under irradiation were also further investigated.These results indicate that NOC-NPs exhibited a remarkable cellular uptake,and then were distributed into the lysosomes.Upon irradiation,NOC-NPs also generated abundant singlet oxygen to destroy lysosomal membranes and translocated into the cytoplasm,thereby causing efficient damage against cancer cells through PDT-synergized PTT.Chapter 4:The in vivo biological effects were investigated,including biodistribution,photothermal and photodynamic effects at tumor sites,and antitumor efficacy.Finally,the biosafety of NOC-NPs was finally evaluated by monitoring the distributions of NOC in normal tissues during 14 days and biochemical markers in bloods during 28 days.These results show that NOC-NPs showed an excellent ability to cause the tumor ablation,together with negligible toxicity.In summary,the NOC-loaded nanoparticles with unique light conversion effects were prepared and characterized.We further performed their in vitro cell studies and in vivo antitumour efficacy in details.According to the content of this work,we hope to provide some new strategies for the exploration of photosensitizers in future.