Applications Of Metal-Organic Framework Complexes In Multimodality Tumor Theranostics

Metal Organic Frameworks(MOFs)have been developed as porous carriers for biomedical imaging and drug delivery in the past two decades.Unlike traditional zeolites,the easily tunable physicochemical properties provide the MOFs with the desired functions,even towards some difficult cases.The flexible framework of MOFs,a benefit from the assembly by metal nodes and organic linkers,enables for their controllable release and degradation.Many works have revealed the potential applications of MOFs in biomedical imaging,since the?electrons in organic linkers contribute greatly to fluorescence,while the metal nodes serve as the contrast agents of CT or MRI.In this work,a series of Au loaded MOFs were synthesized and further used for real-time quantitative analysis of intracellular GSH level.Different linear range can be acquired by altering the size of gold and MOF particles,or adjusting the proportion of 2-aminoterephthalic acid/1,4-benzenedicarboxylate linkers,which is also observed on fluorescein isothiocyanate attached Au-MOFs.Further study reveals that the flexible molecular chain of GSH with the-COOH/NH₂-and-SH terminal may readily tie on relevant gold nanoparticles(Au NPs)through its NH₂-/-COOH groups,which then restricts the intra-molecular motions of fluorescence probes and thus induces marked fluorescence enhancement.Based on these observations,the intracellular GSH level of different cells including L02 cells,Hela and U87 as well as Hep G2 cancer cells can be rapidly evaluated by these Au-MOF probes.Metal-organic frameworks possess the tremendous potential in biomedical areas for their particular structure.Thus,we explored Fe²⁺-adsorbed nano zeolitic imidazolate framework-8(ZIF-8)for in vivo multimodal imaging of cancerous cells for early diagnosis of target cancers.We synthesized ZIF-8 nanoparticles of 90 nm,our observations demonstrate that Fe²⁺can substitute the Zn²⁺in the metal nodes of ZIF-8.The Fe²⁺-adsorbed ZIF-8 can accumulate in tumor region via enhanced permeability and retention(EPR)effect,and readily transform to fluorescence zinc oxides and super paramagnetic Fe₃O₄ under the synergistic reaction of reactive oxygen species(ROS),glutathione(GSH)and weak acids.It is evident that the formation of the nanoclusters only occurred in cancerous cells,and does not take place in normal cells,which could be attributed to the different ROS levels and specific micro-environment in tumor and normal cells.This raises the possibility for the Fe²⁺-adsorbed zeolitic imidazolate framework to act as the promising agents for the in vivo multimodal imaging of cancers in their early stage.Despite all the efforts to develop an ideal technology for cancer treatment,vital parameters,such as reducing the adverse effects and improving treatment efficiency,still require significant improvement.For this purpose,the rational design of a smart stimuli-responsive and fully biodegradable delivery system is of great significance.We encapsulated black phosphorous quantum dots(BPQDs)and S-Nitrosoglutathione(GSNO)into HKUST-1@MIL-100 for the multimodal therapy of tumors.Since BPQD easily degrades in most of the saline solutions and at higher temperatures,the external growth of MOFs subjects to the 2D structure of BPQD,and the ultra-small particle size and homogeneity of Cu-based MOFs are difficult to control in conventional methods.To solve these issues,we proposed a"framework exchange"strategy by using ZIF-8nanoparticles as a sacrificial template.In cancerous cells,the GSH and ROS levels trigger the sequential reaction to rebuild the redox equilibrium and stimulate the continuous production of NO and hydroxyl radicals.As a result,the MOFs serve not only as carriers and contrast agents but also as the catalysts for the generation of NO and·OH,which results in a maximum atomic efficiency.Finally,the nanosystem completely degrades into small molecules and is excreted from the body.