Novel Nanosystems For Tumor-associated MiRNAs Imaging And Photodynamic Therapy In Living Cells

Cancer,being among the primary contributors to human fatality,poses a weighty risk to the survival of individuals.Micro RNAs(mi RNAs)are a key factor in cancer theranostic,whose aberrant expression is closely associated with cancer development and progression.Precise monitoring of changes in mi RNA concentrations can provide valuable information for cancer diagnosis,targeted therapy,and prognostic monitoring.Currently,multiple techniques have been developed for mi RNA detection,which encompass quantitative real-time polymerase chain reaction(q RT-PCR),Northern blotting technique,microarrays,fluorescent probes,surface-enhanced Raman scattering(SERS)and so on.Among them,fluorescence analysis has the advantages of high sensitivity,good selectivity,and wide linear range of working curve,which offer valuable ideas for the development of a comprehensive theranostic platform.DNA molecular probes also have received wide attention due to their sequence programmability.However,DNA molecular probes face challenges such as low delivery efficiency and instability in complex biological environments,hindering their further application in live cells.Consequently,the development of multifunctional nanocarriers to enhance delivery efficiency and stability of DNA molecular probes,remains one of major challenges in the current field of cancer diagnosis and treatment.With advancements in nanotechnology,researchers have developed a number of highly efficient nanoprobes based on nanocarriers,which hold enormous potential for precision and personalization in cancer treatment.Amidst the numerous types of nanomaterials,nanoscaled metal organic frameworks(NMOFs)possess tunable size and abundant modification sites,providing the space for simultaneous assembly of signal recognition units and drugs.Therefore,NMOFs are extensively employed in the field of cancer theranostic.In this paper,fluorescent nanoprobes and theranostic platforms have been constructed based on NMOFs as versatile nanocarriers for precise recognition of cancer cells and photodynamic therapy.The specific research content is as follows:(1)A two-photon(TP)fluorescent nanoprobe based on the catalytic hairpins assembly(CHA)and metal-organic framework for signal amplified imaging of micro RNA in living cells and tissuesAiming at the challenge of low accuracy and sensitivity of low abundance mi RNA detection in living cells,we have developed a novel two-photon nanoprobe(TP-CHA-MOFs)by combining MOF(Ui O-66)with DNA probes.The nanoprobe has excellent loading capacity of nucleic acid molecules,biostability and biocompatibility.The nanoprobe achieves the amplification detection of intracellular mi RNA and amplified imaging of mi RNA in deep tumor tissues.The strategy proposed in this study offers a novel approach for the application of programmable DNA reactions in the field of medical diagnosis.(2)A theranostic system based on multifunctional MOF and DNA logic gates for dual-mi RNA controlled accurate cancer cell recognition and photodynamic therapyThe application of DNA molecular probes in precision medicine is hindered by issues such as off-target effects in the detection of single mi RNAs and low cell entry efficiency.To address these challenges,we have developed a theranostic system(DAPM)that combines photosensitive metal-organic frameworks(PMOFs,PM)with DNA AND logic gates(DA).DAPM has high DNA loading efficiency,stability,and sensitivity.This theranostic system is capable of simultaneously detecting two micro RNAs and performing imageguided photodynamic therapy,which offers a new research approach for the precise diagnosis and treatment of cancers.(3)Functionalized photosensitive metal-organic framework as a theranostic nanoplatform for turn-on detection of Micro RNA and photodynamic therapyThe DNA-MOF system has been demonstrated to be highly practical in various biomedical applications,but the assembly of biomolecules on the MOF surface may result in premature release and unnecessary degradation.Accordingly,we constructed a theranostic nanoplatform(HPMOF)by adsorbing molecular beacons onto PMOFs,and then covered a layer of ZIF-8 on the HPMOF to achieve a dual-layered nanoscale structure(HPMOF@ZIF-8).HPMOF@ZIF-8 not only has high DNA loading capacity and stability,but also enhances intracellular delivery efficiency and lysosomal escape effect.HPMOF@ZIF-8 can identify cancer cells through mi RNA imaging and enable more accurate cancer treatment.