Investigation On The Nanomedicine Applications Of Metal-organic Framworks Hybrid Nanomaterials

Cancer is a leading cause of death worldwide,accounting for millions of death annually and has become one of the major threats to the health of human beings though great efforts have been made.Theranostics which integrate diagnostic and therapeutic moieties into a single platform have become a trend in cancer treatment.Recent advances in cancer therapy have gradually shifted from a focus on monotherapy to multimodal synergistic therapy,based on the cooperative enhancement interactions between two or more treatments,which may result in enhanced(namely '1 + 1>2')therapeutic effects.The realization of multimodal synergistic therapy relies heavily on the integration of multiple therapeutic modalities in a single nanoplatform rather than simple mixing to reinforce their synergistic effects.Metal-organic frameworks(MOFs)have potential applications in biomedical diagnosis and drug delivery due to their large pore volume,large surface area and tunable pore size.Particularly,MOFs-based heterogeneous hybridization may served as an effective methodology for multimodal synergistic therapy as it fuses the advantages of different materials and endows the hybrid materials with novel chemical and physiological properties.1.In the first study,a simple one-pot way is designed to prepare a type of multifunctional metal-organic framework(MOF)-based hybrid nano gels by in situ hybridization of dopamine monomer in the skeleton of Mn3[Co(CN)6]2(MnCo).The resultant Mn3[Co(CN)6]2-polydopamine(MCP)hybrid nanoparticles show enhanced photothermal conversion efficiency in comparison with pure polydopamine or MnCo nanoparticles synthesized under a similar method and,therefore,show great potential for photothermal therapy(PTT)in vivo.The MCP NPs are expected to possess Ti positive magnetic resonance imaging ability due to the high-spin Mn-N6(S =5/2)in the skeleton of MnCo.To improve the therapy efficiency as a PTT agent,the MCP NPs are further modified with functional polyethylene glycol(PEG)and thiol terminal cyclic arginine-glycine-aspartic acid peptide,respectively:the first one is to increase the stability,biocompatibility,and blood circulation time of MCP NPs in vivo;the second one is to increase the tumor accumulation of MCP-PEG NPs and improve their therapeutic efficiency as photothermal agent.Both in vitro and in vivo experiments have witnessed enhanced cell endocytosis and enhanced photothermal therapy efficacy of MCP-PEG-RGD.2.Although large number of MOFs has been discovered,conventional MOF-based nanoplatforms are mainly limited to the sole MOF source with sole functionality.In this study,surfactant modified Prussian blue(PB)core coated by compact ZIF-8 shell(core-shell dual-MOFs,CSD-MOFs)has been reported through heterogeneous nucleation mechanism.With Prussian blue as core,CSD-MOFs are able to serve as both magnetic resonance imaging(MRI)and fluorescence optical imaging(FOI)agents.We show that CSD-MOFs crystals loading the anticancer drug doxorubicin(DOX)are efficient pH and near-infrared(NIR)dual-stimuli responsive drug delivery vehicles.After the degradation of ZIF-8,simultaneous NIR irradiation to the inner PB MOFs continuously generate heat that kill cancer cells.Their efficacy on HeLa cancer cell lines is higher compared with the respective single treatment modality,achieving synergistic chemo-thermal therapy efficacy.In vivo results indicate that the anti-tumor efficacy of CSD-MOFs@DOX+NIR was 7.16 and 5.07 times enhanced compared to single chemo-the rapy and single thermal-therapy respectively.Our strategy opens new possibilities to construct multifunctional theranostic systems through integration of two different MOFs.3.As we know,traditionnal chemotherapy drugs have serious long-term toxicity to healthy tissue and body.Dihydroartemisinin(DHA)has been investigated in cancer therapy for its reactive oxygen species(ROS)based cytotoxicity originated from interacting with ferrous ions that may eliminate the multidrug resistance commonly associated with conventional chemotherapy drugs.However,synchronously delivery of hydrophobic DHA and ferric ions into tumor cells remains a major challenge.We reported a multifunctional drug-delivery system that shows both magnet targeted and pH-responsive drug release properties.Fe3O4@C nanoparticles were introduced as core and coated with MIL-100(Fe)MOFs shell through a layer-by-layer method to generate core-shell Fe3O4@C@MIL-100(Fe)(FCM)hybrid nanoparticles.Middle carbon layer with embedded small carbon dots serves as fluorescence imaging agent.When exposed to acidic conditions,such as tumor microenvironment,the outer MOFs would degrade and release DHA and ferric ions synchronously.When the pH inside an endosome drops,ferric ions would be reduced to ferrous ions by ferric reductase and other reductive molecules of the cell.Ultimately,ferrous ions reacts with the synchronous released DHA and yield quantity of toxic ROS,to damage proteins and nucleic acid and induce cell death.The as-prepared FCM exerts pH-responsive release of DHA and iron ions and external magnetic field induced cancer therapy.4.The versatile Mn3[Co(CN)6]2@SiO2@Ag core-shell nanocubes(NCs)are prepared by a simple coprecipitation method.Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn3[Co(CN)6]2?SiO2 through S-Ag bonding are fabricated in ethanol solution by reducing silver nitrate(AgNO3)with NaBH4.The nanocubes possess T1-T2 dual-modal magnetic resonance imaging(MRI)ability.The inner MOFs Mn3[Co(CN)6]2 exhibits bright two-photon fluorescence(TPF)imaging when excited at 730 nm.Moreover,the TPF imaging intensity displays 1.85-fold enhancement after loading of Ag nanoparticles.Besides,the sample also has multicolor fluorescence imaging ability under 403-,488-and 543 nm single photon excitation.The as-synthesized Mn3[Co(CN)6]2@SiO2@AgNCs show a DOX loading capacity of 600 mg/g and exhibited excellent ability of NIR-responsive drug release and photothermal therapy(PTT)which induced from the relative high absorbance in NIR region.The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency.The multimodal treatment and imaging could lead to this MOFs-Ag hybrid nanomaterial a potential multifunctional system for biomedical diagnosis and therapy.