Aqueous-phase synthesis of upconversion metal-organic frameworks for ATP-responsive in situ imaging and targeted combinational cancer therapy

Herein,the nanoscaled ATP-responsive upconversion metal-organic frameworks(UCMOFs)are aqueousphase synthesized for co-delivery of therapeutic protein cytochrome c(Cyt c)and chemodrugs doxorubicin(DOX),achieving targeted combinational therapy of human cervical cancer.The UCMOFs are rationally fabricated by growing ZIF-90 on mesoporous silica-coated upconversion nanoparticles(UCNPs),in which the ZIF-90 layer attenuates the upconversion luminescence(UCL)and the rigid frameworks increase the stability of encapsulated proteins.Once the UCMOF@DOX/Cyt c are internalized into HeLa cells via specific recognition of sgc8 aptamers,the intracellular ATP triggers the dissolution of ZIF-90 into Zn^(2+),which facilitates not only the release of Cyt c and DOX but also the restoration of UCL for real-time monitoring of drug release.It has been demonstrated that the therapeutic efficacy is greatly improved by the combination of caspase-mediated apoptosis activated by Cyt c(protein therapeutics),DNA fragmentation induced by DOX(chemotherapy),and Zn;-promoted generation of reactive oxygen species(ROS)(oxidative stress).Overall,our proposed multifunctional UCMOFs provide an effective platform for targeted combinational cancer therapy and in situ imaging,which hold great promise in biomedical and clinical applications.

A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules

In situ tracking and localization of ubiquitous bioactive small molecules(BSMs)within their native habitats is particularly challenging because of their low-molecular weight and widespread distribution properties.We report the proof of concept of a synchronous in situ imaging strategy,whereby the representative BSM amino-biothiols(ABs)mediate activation of the selflocalizable probe HYPQS,thereby releasing insoluble emissive precipitates to afford holistic distribution information of ABs.Notably,three organelle-targetable ABs inhibitors were innovatively fabricated for directed clearance of ABs in particular organelles,providing a powerful aid for HYPQS to achieve programmed in situ tracking of ABs in different organelles“on demand”.Biological transmission electron microscopy images confirmed that this probe released insoluble emissive precipitates at the reaction sites,which is of primary importance for achieving synchronous in situ tracking of BSMs.Furthermore,the probe HYPQS was successfully applied to monitor the dynamic changes in the endogenous ABs pool during diverse cell events.This strategy opens a promising avenue for investigating the undiscovered functional mechanism of local BSMs in relevant biological processes.

Recent Progress in Metallurgical Bonding Mechanisms at the Liquid/Solid Interface of Dissimilar Metals Investigated via in situ X-ray Imaging Technologies

The liquid/solid(L/S)interface of dissimilar metals is critical to the microstructure,mechanical strength,and structural integrity of interconnects in many important applications such as electronics,automotive,aeronautics,and astronautics,and therefore has drawn increasing research interests.To design preferential microstructure and optimize mechanical properties of the interconnects,it is crucial to understand the formation and growth mechanisms of diversified structures at the L/S interface during interconnecting.In situ synchrotron radiation or tube-generated X-ray radiography and tomography technologies make it possible to observe the evolution of the L/S interface directly and therefore have greatly propelled the research in this field.Here,we review the recent progress in understanding the L/S interface behaviors using advanced in situ X-ray imaging techniques with a particular focus on the following two issues:(1)interface behaviors in the solder joints for microelectronic packaging including the intermetallic compounds(IMCs)during refl ow,Sn dendrites,and IMCs during solidification and refl ow porosities and(2)growth characteristics and morphological transition of IMCs in the interconnect of dissimilar metals at high temperature.Furthermore,the main achievements and future research perspectives in terms of metallurgical bonding mechanisms under complex conditions with improved X-ray sources and detectors are remarked and discussed.