Novel Nanomaterials For Electrochemical Biosensor And Cancer Therapy

Cancer has become one of the major threats to human health.Compared with normal cells,cancer cells have three major characteristics including infinite proliferation,can be changed and easy to transfer.Cancer cells can proliferate indefinitely and destroy normal tissue.Early diagnosis and treatment of cancer is the key to improve the survival rate of cancer patients and has been a hot topic in related fields.However,conventional diagnostic techniques often suffer from the shortcomings of false-positive diagnostic results and toxic side effects during the treatment with cancer.Electrochemical sensing technology is a combination of electrochemical response and biomolecule recognition technology,with a simple device,low cost,high sensitivity and good stability.So the detection of cancer-related biomolecules by electrochemical method received wide attention.On the other hand,nanomaterials are widely used in clinical diagnosis and treatment,drug analysis,energy and environment and other fields because of its small size,good biocompatibility,unique physical and chemical properties,easy to modify,etc.Based on the above research background,this paper develops new functional nanomaterials which could be applied in the field of electrochemical biosensing,and further explores its application in early diagnosis and treatment of cancer.The main contents were described as below:1.Simultaneous Detection of Tumor Cell Apoptosis Regulators Bcl-2 and Bax through a Dual-Signal-Marked Electrochemical ImmunosensorBcl-2 family plays an important role in the regulation of apoptosis.During them,B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax)are often used to monitor the apoptosis of tumor cells and evaluate cancer drug effect.In this work,a novel sandwich-type dual-signal-marked electrochemical biosensor was fabricated for simultaneous detection of Bcl-2 and Bax proteins.Reduced graphene oxide(RGO)layers were used as substrate to immobilize Bcl-2 and Bax antibodies for further capturing target antigens(Bcl-2 and Bax antigens).Then,CdSeTe@CdS quantum dots(QDs)and Ag nanoclusters(NCs)with antibody modification and mesoporous silica amplification were used as signal probes,which were proportional to the amount of Bcl-2 and Bax antigens.The Bcl-2 and Bax proteins were determined indirectly by the detection of oxidation peak currents of Cd and Ag using anodic stripping voltammetry(ASV).The designed electrochemical immunoassay exhibited an ultralow detection limit,reproducibility and stability for Bcl-2 and Bax detection.The biosensor was further introduced to investigate Bcl-2 and Bax expressions from nilotinib-treated chronic myeloid leukemia K562 cells.The ratio of Bax/Bcl-2 was further calculated for evaluation of its drug effect and apoptosis level.This novel electrochemical immunosensor also provides a promising tool for apoptosos research and the cancer treatment.2.DNA Polymerase-Directed Hairpin Assembly for Targeted Drug Delivery and Amplified BiosensingDue to the predictable conformation and programmable Watson-Crick base-pairing interactions,DNA has proven to be an attractive material to construct various nanostructures.Herein,we demonstrate a simple model of DNA polymerase-directed hairpin assembly(PDHA)to construct DNA nanoassemblies for versatile applications in biomedicine and biosensing.The system consists of only two hairpins,an initiator and a DNA polymerase.Upon addition of aptamer-linked initiator,the inert stems of the two hairpins are activated alternately under the direction of DNA polymerase,which thus grows into aptamer-tethered DNA nanoassemblies(AptNAs).Moreover,through incorporating fluorophores and drug-loading sites into the AptNAs,we have constructed multifunctional DNA nanoassemblies for targeted cancer therapy with high drug payloads and good biocompatibility.Taking advantage of easy preparation and high loading capacity,the PDHAs are readily extended to the fabrication of a label-free biosensing platform,achieving amplified electrochemical detection of microRNA-21(miR-21)with a detection limit as low as 0.75 fM and a dynamic range of 8 orders of magnitude.This biosensor also demonstrates excellent specificity to discriminate the target miR-21 from the control microRNAs and even the one-base mismatched one and further performs well in analyzing miR-21 in MCF-7 tumor cells.The proposed PDHA strategy demonstrates significantly current and potential applications in both cancer diagnosis and treatment.