Croconaine Dye Based Self-assembled Nanomaterials For Tumor Theranostic Applications

The rapid development of molecular imaging technology and nanotechnology provides new ideas for precision medicine.Functional design and preparation of multifunctional molecular probes for diagnosis and treatment have become the focus of current research.Therefore,this paper focuses on functional modification of croconaine dyes and their self-assembled nanomaterials with near-infrared light absorption and fluorescence,as well as ultra-high photothermal conversion efficiency and light stability,and construction of integrated molecular probes for diagnosis and treatment,as well as its application in diagnosis and treatment of tumors.Due to the poor water solubility of croconaine dye,it tends to aggregate with each other,which limits their biological applications.Therefore,a series of different PEG chain-modified croconaine nanoparticles were synthesized as theranostic agents.Nanoparticles of different sizes can be obtained by chemical modification of croconaine dyes with different lengths of polyethylene glycol(mPEG5k,mPEG2k,mPEG132)by self-assembly.Among them,nanoparticles with the smallest particle size and the strongest fluorescence can be obtained after PEG5K modification,which show the highest uptake in tumors.Because of the strong absorption of croconaie dye in the near infrared region,it can be used in photoacoustic imaging and photothermal therapy.Therefore,we applied it to the photoacoustic and fluorescence bimodal imaging to guide the photothermal treatment of tumors.In order to improve the tumor uptake,reduce toxic and side effects,we further conjugated RGD peptides targeting integrin receptors on PEG5K-modified ketonic acid dyes and labeled them with radioactive iodine(125I).It can be used for SPECT/CT,photoacoustic,fluorescence three modality imaging guidance of glioma photothermal therapy,and ultimately achieve a multifunctional integrated diagnostic probe preparation,which was easy to achieve clinical translation.Combined photothermal therapy and chemotherapy can play a better cancer therapy effect.In order to further improve its anti-tumor effects,and achieve accurate drug release and reduce the side effects of chemotherapy,we designed a logic gated modular nanocapsule that can achieve programmed drug release for cancer diagnosis and treatment under NIR laser.The croconaine dye and doxorubicin were linked to form a precursor by chemical bonds with both photothermal and pH responses.Finally,the precursor and the free radical initiator were coated by a polymer with a free radical response.Under the irradiation of near-infrared light,precise drug release was achieved at the tumor site.PET/CT imaging was achieved by labeling with 64Cu on the croconaine dye,and photoacoustic imaging was also performed to monitor and guide the treatment of cancer.