Applications Of Inorganic Nanoparticles And Nucleic Acid Nanomaterials In Diagnosis And Targeted Therapy Of Cancer Cells

Tumor is a disease with one of the highest motality rate.Traditional anti-cancer drugs are heavily limited in clinic applications because of their low targeting abilities,weak biocompatibilities,fast metabolic rates,and strong toxicities to healthy tissues and cells.In addition,detection of tumor biomarkers has currently become a popular method of early diagnosis of tumors.However,some problems are high sensitivity and specificity of this detection method.To solve the problems above,in this thesis,based on several kinds of inorganic nanoparticles and nuclear acid nanomaterials,biosensors are developed for detection of tumor biomarkers telomerase and miRNA.In addition,precise controlling of cancer cell-targeting abilities of nanodrugs is investigated through study of targeting ligands and groups to organelles and cancer cells.Main contents of this thesis are described as follows:?1?Constructing a nano-scale biosensor based on telomerase primer DNA strand with specific sequence,which is proved to response to telomerase extracts in vitro and telomerase inside living cells.Telomerase extracted from only 5 cancer cells are detected by this biosensor.Also,telomerase extracted from urine specimens of bladder cancer patients are detected with the clear urine specimen detection rate of100%,and bloody urine specimen detection rate of 89.5%.In addition,real-time detection of telomerase in living cancer cells are successfully carried out by this biosensor.?2?Fluorescent nanodiamonds?FNDs?are combined with Fe₃O₄ magnetic nanoparticles?MNPs?for designing of a biosensor FND-DNA-MNP,due to the special relaxation time signals of FNDs and magnetic fields from MNPs.In the presence of target miR-21?a common-used cancer biomarker?,biosensor FND-DNA-MNP responses to miR-21 with changes of relaxation time signals.Due to the low background of relaxation time signal in human bodies,this biosensor is expected to be used for miR-21 detection in living cells and in vivo with single molecule resolution.?3?Precisely labeling tumor cells targeting ligands,transferrins?Tfs?,at specific sites on surface of DNA origami nanostructures,which are used as drug nanocarriers,to investigate how the distribution of Tfs affect cellular uptake efficiency of DNA nanocarriers.The amounts of Tfs labeled on surface of DNA origami nanocarrier are found to show the strongest influence to cellular uptake efficiency,followed by distance of Tfs,which shows an order of 28 nm>14 nm>>42 nm.In addition,the labeling position of Tfs on surface of DNA origami nanocarrier shows no significant influence to cellular uptake efficiency.?4?Anti-cancer nanodrug selenium nanoparticles?SeNPs?are functionalized with?3-carboxypropyl?triphenylphosphonium bromide?TPP,a mitochondria-targeting group?,so that SeNPs can target at mitochondria,and show much heavier oxidative damages of reactive oxygen species?ROS?to mitochondira.Through this modification,SeNPs show a higher anti-cancer ability,and reduce toxicity to healthy tissues and cells,due to the lower dosage of SeNPs in potential clinic applications.In this thesis,it is expected to construct biosensors of tumor biomarkers with high sensitivity to improve early detection and diagnosis of cancer,and improve cancer-targeting abilities of anti-cancer drugs through founctionalization of organelle-targeting groups and precise modifying of cancer cell-tarting ligands,to reduce toxicities of drugs to healthy cells.