Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies

Homodimeric prodrug-based self-assembled nanoparticles,with carrier-free structure and ultrahigh drug loading,is drawing more and more attentions.Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage.The influence of the linkages on the self-assembly,in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research.Herein,three docetaxel(DTX)homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages.Interestingly,compared with the other two linkages,the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs,thus improving the stability,circulation time and tumor targeting of prodrug nanoassemblies.Besides,the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells.Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells,their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells,which finally“turned the table”.Our study illustrates the crucial role of linkages in homodimeric prodrugs,and gives valuable proposal for the development of advanced nano-DDS for cancer treatment.

Dynamic diselenide bond-enabled liquid crystal elastomer-based two-way shape memory aerogels with weldability and closedloop recyclability

Two-way shape memory polymeric aerogels(2W-SMPAs),with the ability to undergo reversible shape deformation in response to external stimuli,have extensive application in diverse fields such as actuators,sensors,robotics,and other relevant domains.In this study,we introduce a novel approach for fabricating a 2W-SMPA material based on liquid crystal elastomers(LCEs)incorporating dynamic diselenide bonds.The aerogel exhibits liquid crystal phases,excellent compressibility and shape stability,and the mesogens are uniaxial-oriented along the stretching direction.By capitalizing on the dynamic diselenide bonds,the LCEbased aerogel demonstrated remarkable reprogrammability,weldability,and recyclability through thermal reorganization.The shape-programmed aerogel sample exhibits reversible shrinking deformation during the heating and cooling cycles,ultimately achieving a maximum shrinkage ratio of 26.1%.Moreover,the LCE-based aerogel's porous structure and monodomain orientation effectively enable the adsorption of the photothermal dye DR1 and facilitated the reversible photothermal-induced shape deformation when exposed to 520 nm light irradiation.These findings reveal the potential application of this innovative LCE-based aerogel material,enabled by dynamic diselenide bonds,in various areas including control devices,soft actuators,and other diverse fields.

Engineering Reversible Hydrogels for 3D Cell Culture and Release Using Diselenide Catalyzed Fast Disulfide Formation

Hydrogels crosslinked by dynamic covalent bonds can effectively mimic the viscoelastic properties of native extracellular matrix and have been widely explored for 3D cell culture.Disulfide is one of the most common dynamic bonds in biological systems whose formation and cleavage are catalyzed by a set of dedicated enzymes.However,in vitro formation of disulfide bonds is a slow process and requires harsh catalysts.Therefore,it is difficult to use disulfide crosslinked hydrogels for cell culture.n this work,we show that disulfide bonds can be formed by thiol-diselenide(Dise)exchange under blue light llumination.This reaction is fast,reversible,and biocompatible.Moreover,residual diselenide in the hydrogel network can also accelerate thiol-disulfide exchange reactions leading to faster cell release from the hydrogels upon the addition of thiol-containing agents.We anticipate that disulfide crosslinked hydrogels catalyzed by diselenide can find broad biomedical applications,such as cell culture,celldelivery,and drug-controlled release.

The dynamic covalent reaction based on diselenide-containing crown ether irradiated by visible light

A novel diselenide-containing crown ether(BC7Se_(2))was fabricated,which can polymerize to form cyclic oligomers through intermolecular dynamic covalent reaction by irradiation of visible light.The size and distribution of oligomers are related to the monomer concentration.The decomposition reaction of oligomers is controlled by topology and solvents.Furthermore,potassium cation can inhibit the polymerization of BC7Se_(2)and accelerate the decomposition of oligomers.