50906-77-9Relevant articles and documents
A tri-responsive and fast self-healing organogel with stretchability based on multiple dynamic covalent bonds
Ren, Shujing,Liang, Huiqin,Sun, Panpan,Gao, Yanan,Zheng, Liqiang
, p. 1609 - 1614 (2020)
Smart self-healing materials have attracted much attention due to their promising applications in biological and medical fields. Here, a tri-responsive and fast self-healing organogel based on a boronate ester bond, an acylhydrazone bond and a disulfide bond was prepared from polyvinyl alcohol (PVA), 4-formylphenylboronic acid (FPBA), and 3,3′-dithiobis (propionohydrazide) (DPH). PVA was selected as a gel skeleton to improve the mechanical property of the organogel. A tensile test indicated that the obtained organogel is highly stretchable. Due to the dynamic nature of reversible covalent chemistry, the organogel can respond to pH, glucose and redox to undergo gel-sol phase transition. Microscopy observation and tensile tests further indicate that the organogel can self-repair without external stimuli.
Modulating Thiol p Ka Promotes Disulfide Formation at Physiological pH: An Elegant Strategy to Design Disulfide Cross-Linked Hyaluronic Acid Hydrogels
Bermejo-Velasco, Daniel,Azémar, Alice,Oommen, Oommen P.,Hilborn, J?ns,Varghese, Oommen P.
, p. 1412 - 1420 (2019/03/02)
The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors, and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants, and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as l-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 × 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 × 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-l-cysteine substrate (k1 = 0.51 × 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys); and 8.1 for HA-thiol (HA-SH) derivatives, respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 min or 10 h, respectively, at pH 7.4. After completion of cross-linking reaction, both gels demonstrated a storage modulus G′ ≈ 3300-3500 Pa, which indicated comparable levels of cross-linking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.
Smart low molecular weight hydrogels with dynamic covalent skeletons
Sun, Panpan,Ren, Shujing,Liu, Fenglin,Wu, Aoli,Sun, Na,Shi, Lijuan,Zheng, Liqiang
, p. 6678 - 6683 (2018/08/28)
We report a new strategy for fabricating a smart low molecular weight hydrogel based on dynamic covalent chemistry from a bola-type supra-gelator, which was facilely fabricated in situ from two non-assembling building blocks, (3-(2-(4-formylphenoxy) ethyl)-1-methyl imidazolium bromide, MA) and (3,3′-dithiobis (propionohydrazide), DSPDZ), through dynamic acylhydrazone bonding. The obtained low molecular weight hydrogels exhibited redox-responsive and controllable self-healing properties. The role of dynamic covalent bonding in the formation of smart hydrogels is revealed in this study, which provides a simple and bottom-up method for constructing smart low molecular weight hydrogels.
Preparation, characterization, and biocompatibility evaluation of poly(Nε-acryloyl-l-lysine)/hyaluronic acid interpenetrating network hydrogels
Cui, Ning,Qian, Junmin,Xu, Weijun,Xu, Minghui,Zhao, Na,Liu, Ting,Wang, Hongjie
, p. 1017 - 1026 (2015/10/29)
In the present study, poly(Nε-acryloyl-l-lysine)/hyaluronic acid (pLysAAm/HA) interpenetrating network (IPN) hydrogels were successfully fabricated through the combination of hydrazone bond crosslinking and photo-crosslinking reactions. The HA hydrogel network was first synthesized from 3,3′-dithiodipropionate hydrazide-modified HA and polyethylene glycol dilevulinate by hydrazone bond crosslinking. The pLysAAm hydrogel network was prepared from Nε-acryloyl-l-lysine and N,N′-bis(acryloyl)-(l)-cystine by photo-crosslinking. The resultant pLysAAm/HA hydrogels had a good shape recovery property after loading and unloading for 1.5 cycles (up to 90%) and displayed a highly porous microstructure. Their compressive moduli were at least 5 times higher than that of HA hydrogels. The pLysAAm/HA hydrogels had an equilibrium swelling ratio of up to 37.9 and displayed a glutathione-responsive degradation behavior. The results from in vitro biocompatibility evaluation with pre-osteoblasts MC3T3-E1 cells revealed that the pLysAAm/HA hydrogels could support cell viability and proliferation. Hematoxylin and eosin staining indicated that the pLysAAm/HA hydrogels allowed cell and tissue infiltration, confirming their good in vivo biocompatibility. Therefore, the novel pLysAAm/HA IPN hydrogels have great potential for bone tissue engineering applications.
Co-delivery of doxorubicin and P-glycoprotein siRNA by multifunctional triblock copolymers for enhanced anticancer efficacy in breast cancer cells
Xu, Minghui,Qian, Junmin,Suo, Aili,Cui, Ning,Yao, Yu,Xu, Weijun,Liu, Ting,Wang, Hongjie
, p. 2215 - 2228 (2015/04/27)
Combined treatment of chemotherapeutics and small interfering RNAs (siRNAs) is a promising therapy strategy for breast carcinoma via their synergetic effects. In this study, to improve the therapeutic effect of doxorubicin (DOX), novel triblock copolymers, folate/methoxy-poly(ethylene glycol)-block-poly(l-glutamate-hydrazide)-block-poly(N,N-dimethylaminopropyl methacrylamide) (FA/m-PEG-b-P(LG-Hyd)-b-PDMAPMA), were synthesized and used as a vehicle for the co-delivery of DOX and P-glycoprotein (P-gp) siRNA into breast cancer cells. The triblock copolymers were synthesized by a combination of ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride using cystamine-terminated heterotelechelic PEG derivatives possessing folate or methoxy end groups (FA/m-PEG-Cys) as initiators and reversible addition-fragmentation chain transfer polymerization of N,N-dimethylaminopropyl methacrylamide followed by hydrazinolysis. The successful synthesis of the copolymers was confirmed by 1H NMR and gel permeation chromatography. DOX was covalently conjugated onto the poly(l-glutamate-hydrazide) blocks via a pH-labile hydrazone linkage, and the DOX-conjugated triblock copolymers could self-assemble into nanoparticles in aqueous solutions. P-glycoprotein (P-gp) siRNA was then bound to the cationic poly(N,N-dimethylaminopropyl methacrylamide) (PDMAPMA) blocks through an electrostatic interaction, resulting in the formation of spherical nanocomplexes with an average diameter of 196.8 nm and a zeta potential of +28.3 mV. The in vitro release behaviors of DOX and siRNA from the nanocomplexes were pH- and reduction-dependent, and the release rates were much faster under a reductive acidic condition (pH 5.0, glutathione: 10 mM) simulating the intracellular endo-lysosomal environment of cancer cells compared to physiological conditions. The fast payload release rates were closely related to both the glutathione-triggered detachment of PEG blocks from the nanocomplex surface and the pH-sensitive cleavage of hydrazone linkages. FA-decorated nanocomplexes showed higher cellular uptake efficiency and cytotoxicity against MCF-7 cells than FA-free nanocomplexes, as confirmed by confocal laser scanning microscopy, transmission electron microscopy, MTT and flow cytometry analyses. Our results demonstrated that the multifunctional triblock copolymer-mediated co-delivery of DOX and P-gp siRNA might be a new promising therapeutic strategy for breast cancer treatment. This journal is
Orthogonal or simultaneous use of disulfide and hydrazone exchange in dynamic covalent chemistry in aqueous solution
Rodriguez-Docampo, Zaida,Otto, Sijbren
supporting information; experimental part, p. 5301 - 5303 (2009/03/11)
Hydrazone and disulfide exchange have been combined in a single system, but can be addressed independently: by adjusting the pH of the solution from acidic to mildly basic it is possible to switch from exclusively hydrazone exchange to exclusively disulfide exchange, while at intermediate pH both reactions occur simultaneously. The Royal Society of Chemistry.
