| Malignant tumor,namely cancer,is a major disease that seriously affects human health,which is originated from epithelial tissue in medicine.As known,cancer has the biological characteristics of abnormal cell differentiation and proliferation,uncontrolled growth,invasion and metastasis,which can be divided into carcinogenesis,cancer promotion and evolution.It is closely related to heredity,acquired living habits,growth environment and other factors.With the progress of society,human beings have paid more attention to their own health than ever before,which also puts forward higher requirements for medical researchers.According to public information,the situation of cancer prevention and control in China is very severe.In recent twenty years,the incidence rate of cancer in China has been gradually increasing year by year and the patients are getting younger.Therefore,how to make a more accurate and rapid judgment of cancer has been widely concerned.Nucleic acid probes are used to detect specific nucleic acid sequences by using the principle of nucleic acid molecular hybridization.When one of the hybridized double-stranded chains is labeled with a detectable substance to make a probe,it can identify and detect another complementary chain.Because of the specific recognition,it has high specificity.In recent years,with the continuous development of nanotechnology,nanomaterials have become the focus of social attention.They have the advantages of small size effect,quantum size effect,surface and interface effect and macroscopic quantum tunneling effect.Therefore,functional nucleic acid nanoprobes have been prepared by combining nucleic acid probes with nanomaterials for cancer imaging.With the advantages of high sensitivity,fast response,strong stability,simple and convenient,they have been widely used in biomedical and other fields.Based on metal organic framework（MOF）and covalent organic framework（COF）,we designed and constructed two functional nucleic acid nanoprobes for high sensitivity detection of m RNA in tumor cells.1.As the most popular nucleic acid probes,molecular beacons（MBs）can selectively light up endogenous RNA targets without specific treatment.However,the poor cell permeability and unsatisfied intracellular stability of MBs significantly restricted their detection performance.Herein,we report the encapsulation of MB within a dual-layered metal organic framework nanostructure Ui O66-ZIF8 for enhanced cell imaging.Ui O66-NH2nanoparticles were synthesized as the template for MB loading,ZIF-8 shell was further coated on the surface of Ui O66-MB to ensure its stability and lysosomal escape effect.Taking multi-drug resistance（MDR1）m RNA as a model target,MBs loaded within Ui O66-ZIF8 showed improved lysosomal escape effect compared with MB absorbed on Ui O66-NH2.Therefore,efficient and accurate intracellular MDR1 m RNA imaging was realized with Ui O66-MB-ZIF8.This work presented a new method for the rational regulation of the intracellular performances of MOF-based nanoprobes and will facilitate the further development of powerful nanoprobes for analytical applications.2.We designed a binding-defect amplified modification strategy（BDAM）for the preparation of functionalized COF.Namely,molecules containing multiple reaction sites（such as polymers）were firstly connected with the defects of COF,which could effectively introduce abundant functional groups onto COF.Thereby the defects of COF were successfully“amplified”,which could serve as the powerful bridge for the further connection with other functional moieties.Based on this method,we successfully developed the first example of COF-based spherical nucleic acid probe（SNAP）,by connecting dense amino-terminated hairpin DNA onto a porphyrin COF nanoparticle（NPs）using polyacrylic acid（PAA）as the defect amplifier.The fluorophore on the other end of the hairpin DNA was quenched by the porphyrin COF NPs by proximity-induced fluorescence resonance energy transfer（FRET）.Upon meeting the specific nucleic acid targets,the FRET process was prohibited due to the formation of rigid duplex,which increased the distance between fluorophores and COF NPs.Therefore,the obtained SNAP could effectively light up specific target both in vitro and in living cells,which was successfully employed for cancer cell imaging. |
