MOFs-Based Nanocomposites For Biomarker Analysis And Anti-Tumor Applications

Early diagnosis and efficient therapy are the key factors to prevent cancer and improve the survival rate of patients.Thus,it is vital to develop efficient biomarker sensing methods and therapeutic strategies.Metal-organic frameworks（MOFs）formed by the coordination between metal ions and organic ligands,possess the advantages of large specific surface area,high loading efficiency,easy modification and excellent biodegradable.These excellent properties of MOFs enhance their prospects in the field of biomarker sensing and cancer therapy.However,the functions of MOFs were limited.Therefore,it is important to design multifunctional MOFs-based nanocomposites for sensing,therapy and therapeutic self-monitoring.Based on excellent physical and chemical properties of MOFs,specific recognition ability of functional nucleic acids and anti-tumor properties of drug molecules,four different MOFs-based nanocomposites were designed.These MOFs-based nanocomposites achieved highly sensitive and selective detection of cancer biomarkers and effective tumor therapy,which may provide valuable theory for precise diagnosis,efficient treatment and therapeutic self-monitoring.The main contents are summarized as follows:1.DNA amplifiers functionalized MOFs for simultaneous imaging of multiplexed m RNA in living cellsTo monitor and image multiplexed low-abundance m RNAs in cells,a nanocomposite was constructed by combining an entropy-driven catalytic amplified nucleic acid probe with MOFs.The experimental results show that MOFs can efficiently protect the nucleic acid probes from the nucleases degradation.The use of amplification method of DNA amplifier empowered the probe to detect two kinds of m RNAs with high sensitivity and selectivity both in normal and cancer cells,and to monitor fluctuations of m RNA levels caused by drug stimulation.This work shows great prospects for the study of m RNA-related diseases,apoptotic process as well as drug mechanism.2.TP-DNAzyme functionalized MOFs for two-photon imaging of Zn²⁺in cells and tissuesAbove-mentioned probe was single-photon excited at short wavelengths,with shortcomings such as phototoxicity,serious interference from intracellular autofluorescence and poor penetration depth,which limited their intracellular applications.Thus,a two-photon-based MOFs nanoprobe with the ability of signal amplification were constructed by integrating the two-photon fluorophore modified DNAzyme on the surface of MOFs nanocarriers.The nanoprobe was successfully applied for highly sensitive two-photon imaging of Zn²⁺in cells and deep tissues as well as monitoring H₂O₂-induced apoptotic signals.3.A biomimetic MOFs-based nanoplatform for enhanced chemodynamic therapyTo improve targeting and therapeutic efficiency of nanodrugs,a cancer cell membrane-biomimetic MOFs nanoplatform was developed for efficient chemodynamic therapy（CDT）.In this study,the biomimetic MOFs nanoplatform possess targeting ability to homologous tumor cells and CDT ability through Russell reaction.What’s more,3-amino-1,2,4-triazole（3AT）was introduced to inhibit the activity of catalase,increasing the content of H₂O₂ in living cell.Experimental results show that Cu²⁺of Cu MOFs not only depletes glutathione,but also catalyzes the ¹O₂production from the peroxidization product hydroperoxides-TCPP by H₂O₂.In vitro and in vivo results both demonstrate that the cancer cell membrane confers efficient homologous targeting and immune escape capabilities on MOFs nanoplatform.Meanwhile,the introduction of exogenous 3AT increases the intracellular H₂O₂accumulation and enhances ¹O₂ production efficiency,resulting in an enhanced CDT.4.Multifunctional MOFs-based nanocomposites for chemotherapy and therapeutic effect monitoringIt is very important to develop a multifunctional nanoprobe with simultaneous therapy and therapeutic self-monitoring.Here,a multifunctional MOFs-based composite was constructed by loading camptothecin,carbon dots（CDs）and aptamer probe.In this system,CDs was used as the mitochondrial membrane potential recognition unit and aptamer was employed as Cyt c recognition unit.This nanocomposite realized high chemotherapy and dynamically monitoring of two apoptotic signals.Furthermore,this strategy expanded the application of functionalized MOFs and also provided a new strategy for the precise monitoring of cancer treatment efficacy.