The Preparation And Application Of Nanoscale Metal-organic Frameworks With Core-Shell/Hollow Structure

Cancer seriously threatens the health of human beings and brings heavy burden to patients and their families.How to conquer cancer has been a great challenge in the medical community.The emergence of nanomedicine has provided a novel approach for tumor diagnosis and treatment.Nanoscale metal-organic frameworks（nMOFs）exhibit excellent performance in drug delivery due to their highly porous structures and good biocompatibility.Moreover,the versatile and tunable components of nMOFs allow themselves to be designed and developed into potential nano-drugs.Therefore,nMOFs have shown great promise in the field of cancer theranostics.The combination of nMOFs with other functional materials to obtain the composites with collective properties can overcome the limitations of single component and integrate multiple functions into one system,thereby showing remarkable superiority in specific applications.Meanwhile,nMOFs with hollow structure（n HMOFs）not only inherit the merits of nMOFs,but also have additional advantages from the hollow structure,which provide a better platform for various functional applications.At present,the research of n HMOFs is still in its infancy.Their preparation is not yet mature and remains a considerable challenge,which hinders their practical applications.Hence,more efforts should be devoted to develope nMOFs-based composites and n HMOFs,and explore their potential applications.Based on the above problems and challenges,we have developed a series of effective methods to fabricate nMOFs with core-shell or hollow structure,which then serve as a superior nanoplatform to overcome current deficiencies of cancer therapy,so as to shed new light on tumor diagnosis and therapy.The main research contents are as follows:Part 1:Magnetically guided delivery of core-shell nanocomposites for cancer theranostics.A rational method is reported to construct Fe₃O₄@PCN-224 core-shell composites by in situ growth of PCN-224 MOFs shell on Fe₃O₄ core.The composites are subsequently loaded with Indocyanine green（ICG）,a near-infrared region（NIR）organic dye,to assemble into a multifunctional nanoplatform.Such nanocomposites simultaneously possess magnetic resonance imaging（MRI）and magnetic targeting abilities of Fe₃O₄ core,drug loading capacity and photodynamic properties of PCN-224 shell together with the fluorescence（FL）imaging and photothermal capability of ICG,and thus achieve MR/FL dual-modality imaging-guided combined photodynamic and photothermal therapy of cancer.Fe₃O₄@PCN-224@ICG shows low cytotoxicity,strong MR and FL imaging signal as well as excellent photodynamic and photothermal performance.It also exhibits predominant synergistic efficiency to kill tumor cells under light irradiation.Furthermore,it can be quickly attracted by external magnetic field,implying its good magnetic targeting ability in vivo,and is expected to improve the therapeutic effects of these two local treatments.Part 2:Preparation of nMOFs with hollow structure.We present two new efficient strategies to successfully synthesize hollow-structured nMOFs.In the first method,Fe₃O₄ nanoparticles（NPs）are adopted as sacrificial template,followed by a uniform coating of MOFs shell to form Fe₃O₄@MOF core-shell structures.After acid-etching of Fe₃O₄core,hollow MOFs nanostructures are acquired.The post-etching treatment may cause a poor crystallinity or the collapse of n HMOFs.Therefore,we continue to explore another method by using acid-labile ZIF-8 NPs as sacrificial template.During the growth of MOFs shell on the surface of ZIF-8 NPs,the ZIF-8 core is gradually etched away by the acidic precursor,thus obtaining n HMOFs without a further etching process.This clever approach can simplify the synthesis procedures and avoid altering the crystallinity of product.The above two methods have several advantages including simple synthesis,mild conditions,good repeatability,high purity and structure tunability.This work provides two model strategies for the construction of hollow-structured nMOFs,and greatly facilitates the development and application of n HMOFs.Part 3:oxygen-self-supplied hollow porphyrinic nMOFs for tumor hypoxia relief and enhanced photodynamic therapy.H-PCN-224,a type of hollow porphyrinic nMOFs with a large cavity,is utilized for loading a large amount of perfluorohexane（PFH）,affording H-PCN-224@PFH as self-oxygenated nano-photosensitizers with a loading efficiency of 5.17 u L PFH/mg H-PCN-224.The superior incorporating way of photosensitizers in porphyrinic nMOFs effectively avoids self-quenching.Furthermore,the hollow thin shell structure can shorten the diffusion distance of singlet oxygen（¹O₂）.Most importantly,the high oxygen affinity of PFH can carry more O₂ for ¹O₂generation to combat the hypoxia-mediated resistance of tumors to photodynamic therapy.Therefore,such nano-photosensitizers are expected to overcome the drawbacks of present photodynamic therapy by these three major strategies.H-PCN-224@PFH exhibits good biocompatibility,moderate oxygen loading capacity and strong ability to generate ¹O₂.The order of ¹O₂generation ability is H-PCN-224@PFH>H-PCN-224>PCN-224.Similarly,H-PCN-224@PFH give the best light-activated cell-killing ability in vitro.All results demonstrate that H-PCN-224@PFH can significantly improve the photodynamic efficacy via the"three birds,one stone"strategy,showing great potentials as a promising platform for photodynamic therapy.