Preparation Of Organic Nanomaterials And Application For Diagnosis And Treatment In Deep Tumor

Traditional cancer treatment methods include surgery,radiation therapy and chemotherapy.However,these methods are often associated with high post-operative trauma,side effects and drug dependence.As a new treatment method,phototherapy has received a lot of attention due to its non-invasive,low side effects and lack of drug dependency.Phototherapy mainly includes photodynamic therapy（PDT）and photothermal therapy（PTT）,in which a photosensitiser absorbs light with specific wavelength and sensitizes water or oxygen to produce reactive oxygen species（ROS）for PDT,or releases the absorbed light energy as heat through non-radiative transition for PTT.Photosensitizers play a vital role in the phototherapy process and a good photosensitizer should have the following properties:NIR absorption,high singlet oxygen quantum yield（Φ）,high photothermal conversion efficiency（η）and deep tissue imaging capability.In addition,most photosensitizers can also produce singlet oxygen for sonodynamic therapy（SDT）under the ultrasound,which has greater advantages over PDT for the treatment of deep tumors.This thesis focuses on the design and synthesis of organic nanomaterials and their application for deep tumor therapy.The main research contents are as follows:（1）Chapter 2 is mainly based on an organic small molecule M1 with a donor-π-acceptor（D-π-A）structure,and then prepared into water-soluble nanoparticles M1 NPs.M1 NPs have strong NIR absorption and NIR-II fluorescence emission capabilities.The M1 NPs also have good photothermal properties,with a photothermal conversion efficiency of 77.5%and good photothermal stability.Both in vitro and in vivo experiments showed that M1 NPs have good photothermal therapeutic ability for tumors under 808 nm laser irradiation.Therefore,M1 NPs have good prospects for application in NIR-II fluorescence/photoacoustic imaging-guided deep photothermal therapy.（2）On the basis of M1,Chapter 3 is based on an acceptor-donor-acceptor（A-D-A）type organic small molecule IDCIC with stronger push-pull electron capability and then prepared into water-soluble nanoparticles IDCIC NPs.IDCIC NPs have strong NIR absorption and NIR-II fluorescence emission.In addition,the IDCIC NPs can generate both singlet oxygen and oxygen-independent·OH for PDT under 808 nm laser excitation with a singlet oxygen quantum yield of 9.1%.IDCIC NPs also have good photothermal conversion capability（η=78.9%）and photostability.Therefore,IDCIC NPs can be used for combined NIR-II fluorescence/photoacoustic imaging-guided photodynamic/photothermal therapy.（3）Although NIR already has a certain penetration depth,there are still limitations in the treatment of deep tumors.Sonodynamic therapy has a much greater depth of tissue penetration.Thus,chapter 4 focuses on the application of sonodynamic therapy in cancer treatment.A water-soluble nanocomplex Nb₂C-PVP-PT2 can be obtained by loading the polymer sonosensitiser PT2 on the surface of Nb₂C.Nb₂C is a two-dimensional nanomaterial with a folded surface that can be oxidized and decomposed in the presence of hydrogen peroxide,releasing the sonosensitiser PT2 so that can achieve tumor microenvironment responsive sonodynamic.