Researchs On New Methods For Early Diagnosis And Precious Treatment Of Tumors Based On Biomimetic Nanomaterials

The efficient diagnosis and therapy of cancers is still a hot topic in the relative biomedical areas involving in the disease diagnostics and treatments as well as patient care.Accurate diagnosis and effective treatment are two important aspects of tumor treatment.The first part of this study starts with promising nano-biomimetic materials in the field of biomedicine by using DNA nano-self-assembly technology.Composite bio-mimetic coating-DNA-Ru（II）-chitosan is used to constructed biological sensing interface and functional nucleic acid structure-DNA nanotweezers are used to realize the transduction of biological signal-electrical signal.thus the constructed enzyme-free"ON-OFF"electrochemiluminescence（ECL）biosensor achieved specific and highly sensitive identification,labeling,and rapid detection of tumors biomarkers,overcoming the shortcomings of conventional detection methods,and establishing and developing a new biomedical sensing system for early diagnosis of malignant tumors.The second part creates a controllable,liver cancer-targeted biomimetic biomolecular recognition carrier by constructing a new type of vesicles with specific properties of source materials-endoplasmic reticulum vesicles,which are loaded with small interfering RNAs with special functions（si GRP94）.Thereby an exogenous biological vesicle-drug nanosystem that induces physiological signal regulation-transformation into pathological changes in cancer cells was constructed.The new vesicle-drug nanosystem works as a new biomedical analysis method and realizes the real-time dynamic intracellular membrane transport analysis in vivo.Therefore,it is of great significance in the early treatment of tumors.1 An enzyme-free“ON-OFF”electrochemiluminescence biosensor for ultrasensitive detection of PML/RARαbased on target-switched DNA nanotweezerHerein,an enzyme-free“ON-OFF”electrochemiluminescence（ECL）biosensor for ultrasensitive detection of fusion gene PML/RARαis constructed based on a simple target-switched DNA nanotweezer as hemin concentration controller.In this biosensor,the hemin concentration is primarily controlled by the conversion of“opened-closed”DNA nanotweezers and low concentration hemin is first used as electrochemically regenerable enhancer.In the absence of the target,the nanotweezers are in an opened state which lead to a low concentration of hemin in the solution,resulting in an enhanced Ru（bpy）₃²⁺ECL signal.In the presence of the target,the closed nanotweezers absorbed onto the surface of electrode can capture the hemin,which achieves a high concentration of hemin and then quenches the ECL signal.The developed method achieves ultrasensitive detection of PML/RARαwith a wide linear range from 1 f M to 1 n M and limit of detection as low as 0.125 f M.In addition,the ECL biosensor shows excellent specificity to the other subtypes of PML/RARα（subtype“S”,“V”）,“PML”,and“RARα”.Moreover,due to the high designable character of DNA nanotweezer,this method might provide a pragmatic Ru（bpy）₃²⁺ECL platform for ultrasensitive detection of nucleic acid in the future.2 Multifunctional endoplasmic reticulum vesicles encapsulating si GRP94 trigger CRAC channels activation and cell stress to self–induce apoptosisExisting biovesicles–derived tumor therapy predominantly rely on internal antitumor drugs,rather than the surface functional proteins or small molecules.Here,we present that si GRP94–encapsulated multifunctional endoplasmic reticulum vesicles（si GRP94–ERVs）have a strong ability of disrupting Ca²⁺homeostasis to promote the precise hepatoma cell self–induce apoptosis owing to mandatory activation of calcium release–activated calcium（CRAC）channels.si GRP94–ERVs composed of mannose–rich ERVs for precisely stimulating endoplasmic reticulum stress（ERS）and si GRP94 for gene silence.Specifically,si GRP94–ERVs activated CRAC channels by interaction of calcium sensor STIM1 on ERVs and the modulator ORAI1 on cells,assembling CRAC channels and stimulating ERS.With downregulation of the ERS protective protein GRP94,si GRP94–ERVs aggravated ERS and induced the production of reactive oxygen species（ROS）,activating apoptotic pathways in damaged cells.Thus,results have shown the potential of si GRP94–ERVs as a novel tumor killing strategy that explored a new mechanism of physiological–turn to–pathological state by inducing self–induce cell apoptosis through their Ca²⁺channels and expend to the next–generation,versatile ERVs to precisely regulate cell functions in a broader application.