Photoswitchable Molecular Recognition Enabled by Dithienylethene-Mediated Structural Changes of Dynamic Covalent Hydrazone Bonds

Light-induced recognition,assemblies,and materials are intensive areas of research due to their high spatiotemporal resolution.Herein,we demonstrated photoswitchable molecular recognition via dithienylethene-triggeredreversible structural regulation of dynamic covalent hydrazone bonds.By combining dithienylethenes and cyclic hemiacetals,the photochemical open-ring and closed-ring forms enabled turningoff and on the creation of awide range of hydrazones when desired.Light-induced bidirectional switching between hydrazones and their cyclization structures promoted by a neighboring carboxyl group was further achieved.By taking advantage of reversible structural changes totoggleon andoff the binding pocket,photoswitchable recognitionofmetal ionswas realized.Finally,the construction of an acylhydrazone polymer offered a facile way for light-mediated selective extraction/release.The strategies and results reported here should find applications in many contexts,such asdynamicassemblies,molecular switches,and smart materials.

A glutathione-triggered precision explosive system for improving tumor chemosensitivity

Stimuli-responsive delivery systems hold promise in cancer treatments.However,their application potential has been limited due to undesirable drug leaking during blood circulation and inefficient therapeutic efficacy in tumors,resulting in undesirable therapeutic outcomes.Herein,we have developed a novel redox-sensitive pegylated phospholipid,termed as DOPE-SS-PEG,which can form a glutathione(GSH)-triggered precision explosive system(GPS)for simultaneously improving circulation stability,tumor specificity,and chemosensitivity,leading to explosive anticancer effects.GPS is constructed of liposomal doxorubicin(DOX)functionalized with DOPE-SS-PEG and MnO_(2) nanoparticles,which can protect liposome structure in the presence of serum GSH(20μM),whereas converts to cationic liposome in response to intracellular GSH(10 mM),thereby enhancing circulation stability,tumor specificity,endosomal escape,and cytoplasmic delivery.Importantly,GPS can not only generate oxygen to relieve hypoxia and consequently enhance chemosensitivity,but quench GSH antioxidability to elevate the accruement of intracellular reactive oxygen species(ROS),leading to an explosion of oxidative stress induced cell injury.Particularly,in vivo studies show that GPS selectively accumulates in tumor tissues,effectively inhibits tumor growth,exhibits minimal systemic adverse effects,and consequently prolongs the survival time of tumor-bearing mice.Therefore,GPS is a unique stimuli-responsive treatment with programmed and on-demand drug delivery,as well as explosive therapeutic efficacy,and provides an intelligent anticancer treatment.