Research On Optical/electrical Sensing Analysis Of New Tumor Markers Based On Functionalized Nanomaterials And Amplification Strategies

At present,cancer is a major malignant disease that threatens the healthy life of human beings.Because of the great difference in mortality and clinical cure rates,it has attracted much attention from the society.At present,there are many mature cancer treatment methods,such as chemotherapy,radiotherapy,microwave therapy,etc.,which have been widely used in cancer treatment.However,these treatment methods,while curing cancer cells,can cause damage to normal cells,causing great harm to the patient’s physical and psychological.Secondly,in cancer drug therapy,many anticancer drugs have poor biosolubility,weak targeting,and severe toxic and side effects.Therefore,the development of new cancer prevention and targeted therapies is needed.Tumor markers provide important information for early diagnosis and clinical response to cancer and are key to cancer prevention and detection.The detection results of tumor markers are directly related to the patient’s future chance of survival.At present,there are many methods for clinical detection of tumor markers,but there are two major problems that are poor sensitivity,low specificity,and weak drug delivery,targeting release.The rapid development of functional nanomaterials and optical-electrical technologies has provided new opportunities and ideas for solving the above two major issues.The use of highly sensitive electrochemiluminescence and fluorescence detection methods combined with unique functional nanomaterials creates a novel,low-cost,highly-sensitive and highly-targeted biosensing system for tumors tested.The following is the content of the study:1.Integration of intracellular telomerase monitoring by electrochemiluminescence technology（ECL）and targeted cancer therapy by reactive oxygenspeciesCancer therapies based on reactive oxygen species（ROS）have emerged as promising clinical treatments.Electrochemiluminescence（ECL）technology has also attracted considerable attention in the field of clinical diagnosis.However,studies about the integration of ECL diagnosis and ROS cancer therapy are very rare.Here we introduce a novel strategy that employs ECL technology and ROS to fill the above vacancy.Briefly,an ITO electrode was electrodeposited with polyluminol-Pt NPs composite films and modified with aptamer DNA to capture HL-60 cancer cells with high specificity.After that,mesoporous silica nanoparticles（MSNs）filled with phorbol 12-myristate 13-acetate（PMA）were closed by the telomerase primer DNA（T-primer DNA）and aptamer.After aptamer on MSN@PMA recognized and combined with the HL-60 cancer cells with high specificity,T-primer DNA on MSN@PMA could be moved away from the MSN@PMA surface after extension by telomerase in the HL-60 cancer cells and PMA was released to induce the production of ROS by the HL-60 cancer cells.After that,the polyluminol-Pt NPs composite films could react with hydrogen peroxide（a major ROS）and generate an ECL signal.Thus the intracellular telomerase activity of the HL-60 cancer cells could be detected in situ.Besides,ROS could induce apoptosis in the HL-60 cancer cells with high efficacy by causing oxidative damage to the lipids,protein,and DNA.Above all,the designed platform could not only detect intracellular telomerase activity instead of that of extracted telomerase,but could also kill targeted tumors by ECL technology and ROS.2.Amplified fluorescence detection of serum prostate specific antigen based on metal-dependent DNAzyme assistant nanomachine.An amplified fluorescence biosensing strategy for serum prostate specific antigen（PSA）was developedon the basis of DNAzyme.In presence of cofactor Zn²⁺,Zn²⁺-dependent DNAzyme could cleave thehairpin substrate probes which were dispersed in solution and generate remarkable fluorescent signal.Taking advantage of the magnetic beads as a carrier,one target protein could bring plentiful hairpinsubstrate probes on to the electrode through a sandwich structure（Ab₁/PSA/biotin-Ab₂）.Moreover,during the cleavage process of as formed DNAzyme,DNAzyme did not be destroyed and could furtherreact with other hairpin probes,then generated continuous fluorescent signal.Benefited by thisamplified strategy,the limit of detection（LOD）was low to 0.05 ng m L^-1,which was much lower than our previous reports.This method could be applied to detect different protein biomarkers in serum without corresponding aptamers by changing the corresponding antibodies and thus showed a remarkableprospect in clinical application.