Integrated Research On Multifunctional Rare Earth Upconversion Luminescent Nanomaterials For Cancer Diagnosis And Treatment

Under the excitation of near-infrared light,rare earth luminescent nanomaterials undergo upconversion luminescence process,emitting fluorescence from the UV-visible region to the wavelength of NIR-I,which has the advantages of long luminescence lifetime,adjustable emission spectrum,good light stability,small damage to biological tissue,deep tissue penetration ability,small background fluorescence,high imaging sensitivity and weak photobleaching.Therefore,upconversion nanomaterials are widely used in the detection of tumor markers,biological imaging.Also,they play an important role in tumor theranostic like chemotherapy,photodynamic therapy,photothermal therapy and gene therapy.This work mainly uses multifunctional rare earth luminescent nanomaterials to develop feasible tumor nanotheranostic agents.The specific research work is as follows:1.Construction of an upconversion nanotheranostic agent coated with aptamers for in-situ release of anticancer drugs in the nucleus.Traditional tumor chemotherapeutics are faced with problems such as large drug dosage,strong toxic effects,and easy emergence of drug resistance.Based on these,this work uses upconversion nanotheranostic agent and aptamers to build a stimuli-responsive upconversion nanocarrier to achieve high concentration accumulation of anticancer drugs in the tumor site,with negligible release to the surrounding healthy tissues.In this experiment,the double stranded DNA will be formed by the aptamer chain of proliferating cell nuclear antigen and its complementary strands that are used to load the anticancer drug,doxorubicin.Thus,doxorubicin would be transported into the nucleus to achieve the in-situ release.This will directly induce tumor cell apoptosis with the apoptosis rate of around 90% and no cytotoxicity to normal cells.2.Construction of an upconversion nanotheranostic agent coated with DNA nanoshells to realize chemotherapy and cascaded photodynamic therapy for tumor sites.Photodynamic nanotheranostic agent based on upconversion nanoparticles have attracted great interest to researchers due to their high tissue penetration,weak autofluorescence and low biological toxicity.This work combines multi-color upconversion nanoparticles,thin-layer mesoporous silica loaded with photosensitizers,and stimuli-responsive DNA nanoshells loaded with anticancer drug molecules to achieve a novel responsive chemotherapy and cascaded amplified photodynamic therapy.Via the layer-by-layer assembly method,the designed nanotheranostic agent can achieve site-specific degradation and controlle degradation rate.Compared with traditional "always-on" treatments,this treatment could be triggered to produce stronger tumoricidal effects inside tumors,aiming to achieve cancer therapy with increased anti-tumor efficacy and diminished side effects.3.Construction of upconversion nanoparticles involved optogenetics to realize the regulation of calcium ions in cell membranes and the activation of biological photosensitizers for tumor therapy.Photosensitive proteins and genetic encoding photosensitizers are increasingly being used as optogenetic tools.This work has constructed a novel plasmid that can simultaneously and specifically express photosensitive proteins and bio-photosensitizers that control the release of calcium ions in cancer cells.The upconversion nanoparticles can be specifically fixed to the cell membrane surface by using the interaction between biotin and streptavidin.Under the excitation of near-infrared light,the upconversion nanoparticles can emit 450 nm and 545 nm wavelengths,which can activate the photosensitive protein,causing the internal flow of calcium ions.They will simultaneously activate the bio-photosensitizer to produce reactive oxygen species.In this work,the experimental phenomenon of calcium ions inflowing and producing reactive oxygen species will synergistically cause apoptosis to cancer cells.