72320-38-8Relevant articles and documents
Preparation of amphiphilic copolymers for covalent loading of paclitaxel for drug delivery system
Chen, Wulian,Zhang, Jin Z.,Hu, Jianhua,Guo, Qisang,Yang, Dong
, p. 366 - 374 (2014)
A novel drug-polymer conjugate was prepared by the copper-catalyzed azide-alkyne cycloaddition reaction between an azide-functional diblock copolymer and an alkyne-functional paclitaxel (PTX). The well-defined azide-functional diblock copolymer, poly(ethylene glycol) (PEG)-b-P(OEGEEMA-co- AzPMA), was synthesized via the atom transfer radical polymerization of oligo(ethylene glycol) ethyl ether methacrylate (OEGEEMA) and 3-azidopropyl methacrylate (AzPMA), using PEG-Br as macroinitiator and CuBr/PMDETA as a catalytic system. The alkyne-functional PTX was covalently linked to the copolymer via a click reaction, and the loading content of PTX could be easily tuned by varying the feeding ratio. Transmission electron microscopy and dynamic light scattering results indicated that the drug loaded copolymers could self-assemble into micelles in aqueous solution. Moreover, the drug release behavior of PEG-b-P(OEGEEMA-co-AzPMA-PTX) was pH dependent, and the cumulative release amount of PTX were 50.0% at pH 5.5, which is about two times higher than that at pH 7.4. The in vitro cytotoxicity experimental results showed that the diblock copolymer was biocompatible, with no obvious cytotoxicity, whereas the PTX-polymer conjugate could efficiently deliver PTX into HeLa and SKOV-3 cells, leading to excellent antitumor activity. 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 366-374 The azide-functional diblock copolymer PEG-b-P(OEGEEMA-co-AzPMA) is synthesized, and alkyne-functional paclitaxel is conjugated to it, using click chemistry. The novel paclitaxel-polymer conjugate self-assembles into micellar nanoparticles in aqueous solution, and the loading content of paclitaxel is easily tuned by the feeding ratio. Copyright
Synthesis of amphiphilic block copolymer consisting of glycopolymer and poly(l-lactide) and preparation of sugar-coated polymer aggregates
Obata, Makoto,Otobuchi, Ryota,Kuroyanagi, Tadao,Takahashi, Masaki,Hirohara, Shiho
, p. 395 - 403 (2017)
The block glycopolymer, poly(2-(α-d-mannopyranosyloxy)ethyl methacrylate)-b-poly(l-lactide) (PManEMA-b-PLLA), was synthesized via a coupling approach. PLLA having an ethynyl group was successfully synthesized via ring-opening polymerization using 2-propyn-1-ol as an initiator. The ethynyl functionality of the resulting polymer was confirmed by MALDI-TOF mass spectroscopy. In contrast, PManEMA having an azide group was prepared via AGET ATRP using 2-azidopropyl 2-bromo-2-methylpropanoate as an initiator. The azide functionality of the resulting polymer was confirmed by IR spectroscopy. The Cu(I)-catalyzed 1,3-dipolar cycloaddition between PLLA and PManEMA was performed to afford PManEMA-b-PLLA. The block structure was confirmed by 1H NMR spectroscopy and size exclusion chromatography. The aggregating properties of the block glycopolymer, PManEMA16k-b-PLLA6.4k (Mn,PManEMA = 16,000, Mn,PLLA = 6400) was examined by 1H NMR spectroscopy, fluorometry using pyrene, and dynamic light scattering. The block glycopolymer formed complicated aggregates at concentrations above 21 mg·L?1 in water. The d-mannose presenting property of the aggregates was also characterized by turbidimetric assay using concanavalin A.
Biodegradable microcapsules designed via 'click' chemistry
De Geest, Bruno G.,Van Camp, Wim,Du Prez, Filip E.,De Smedt, Stefaan C.,Demeester, Jo,Hennink, Wim E.
, p. 190 - 192 (2008)
Dextrans modified with alkyne and azide groups through hydrolysable carbonate esters form degradable microcapsules after CuI catalysed 'click' reaction between azides and alkynes yielding triazole cross-links. The Royal Society of Chemistry.
The Synthesis of Triazole Analogues of Antitumor Dehydropyrrolizidine Alkaloids
Pearson, William H.,Bergmeier, Stephen C.,Chytra, Jayne A.
, p. 156 - 159 (1990)
Several mono- and disubstituted 5,6-dihydro-4H-pyrrolotriazoles have been prepared via intramolecular 1,3-dipolar cycloadditions of azides with alkynes.These triazoles are analogues of the antitumor dehydropyrrolizidine alkaloids.
Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery
Wu, Yanjuan,Zhou, Dongfang,Qi, Yanxin,Xie, Zhigang,Chen, Xuesi,Jing, Xiabin,Huang, Yubin
, p. 31972 - 31983 (2015)
Novel intracellular pH, glutathione (GSH) and reactive oxygen species (ROS)-responsive nanoparticles were obtained using mPEG2k-block-redox dual sensitive chain-block-mPEG2k (PRDSP) which was prepared by Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) click polymerization. The disulfide bond, peroxalate ester and triazole units were regularly and repeatedly arranged in the hydrophobic blocks. The disulfide bond was GSH-sensitive and the peroxalate ester structure could be disrupted by acid and hydrogen peroxide. In addition, the triazole units are capable of forming pH-responsive hydrogen bonds. Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM) were used to investigate the pH, GSH and ROS sensitivity of the PRDSP nanoparticles (NPs). The results indicated that the average diameter, size distribution and morphology greatly changed upon adding GSH/H2O2 or modulating the pH. As the preloaded model anticancer drug, doxorubicin (DOX) was quickly released from DOX-loaded PRDSP (PRDSP@DOX) NPs by addition of 10 mM glutathione (GSH), or 10 mM H2O2 or under acidic conditions rather than under physiological conditions. Confocal laser scanning microscopy (CLSM) and flow cytometric analyses revealed that PRDSP@DOX could effectively deliver DOX into the cytoplasm and nucleus of cells. Therefore, PRDSP NPs may be a promising redox heterogeneity-sensitive carrier for efficient and controlled anticancer drug release.
Synthesis of cyclic dendronized polymers via divergent "graft- from" and convergent click "graft-to" routes: Preparation of modular toroidal macromolecules
Laurent, Boyd A.,Grayson, Scott M.
, p. 13421 - 13429 (2011)
Cyclic dendronized polymers represent a new class of polymers which exhibit a donut-like "toroidal" shape. Two previous unreported methods for preparing this architecture, the divergent "graft-from" and the convergent click "graft-to" approaches, are explored and the resulting products fully characterized. This route is particularly attractive because it enables production of exact linear and cyclic dendronized analogues, enabling direct comparison of their physical properties. In this preliminary work, the divergent "graft from" approach appears to lead to materials with broad PDI at high DP, whereas the "graft to" approach yields more well-defined dendronized cyclic polymers at larger DP. On the basis of reports to date, a combination of click cyclization followed by click "grafting to" provides the most versatile route for the synthesis of cyclic dendronized polymers.
Novel reduction-responsive cross-linked polyethylenimine derivatives by click chemistry for nonviral gene delivery
Liu, Jia,Jiang, Xulin,Xu, Li,Wang, Xianmiao,Hennink, Wim E.,Zhuo, Renxi
, p. 1827 - 1835 (2010)
Novel reducible disulfide-containing cross-linked polyethylenimines (PEI-SS-CLs) were synthesized via click chemistry and evaluated as nonviral gene delivery vectors. First, about four azide pendant groups were introduced into a low-molecular-weight (LMW) PEI (1.8 kDa) to get an azide-terminated PEI. Then, click reaction between a disulfide-containing dialkyne cross-linker and the azide functionalized LMW PEI resulted in a high-molecular-weight disulfide-containing cross-linked PEI composed of LMW constitute via a reducible cross-linker. The synthesized polymers were characterized by 1H NMR, FTIR, and size-exclusion chromatography (SEC). It was shown that the obtained disulfide-containing cross-linked PEIs were able to condense plasmid DNA into positively charged nanoparticles. The degradation of the disulfide cross-linked polymers PEI-SS-CLs induced by DTT was confirmed by a gel retardation assay and SEC analysis. In vitro experiments revealed that the reducible PEI-SS-CLs were less cytotoxic and more effective in gene transfection (in both the presence and absence of serum) than the control nondegradable 25-kDa PEI. This study demonstrates that a reducibly degradable cationic polymer composed of LMW PEI cross-linked via a disulfide-containing linker possesses both higher gene transfection efficiency and lower cytotoxicity than PEI (25 kDa). These polymers are therefore attractive candidates for further in vivo evaluations.
Synthesis of AB3-Type miktoarm star polymers with steroid core via a combination of "click" chemistry and ring opening polymerization techniques
Doganci, Erdinc,Gorur, Mesut,Uyanik, Cavit,Yilmaz, Faruk
, p. 3390 - 3399 (2014)
Well-defined AB3-type miktoarm star-shaped polymers with cholic acid (CA) core were fabricated with a combination of "click" chemistry and ring opening polymerization (ROP) methods. Firstly, azide end-functional poly(ethylene glycol) (mPEG), poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(e-caprolactone) (PCL) polymers were prepared via controlled polymerization and chemical modification methods. Then, CA moieties containing three OH groups were introduced to these polymers as the end groups via Cu(I)-catalyzed click reaction between azide end-functional groups of the polymers (mPEG-N3, PMMA-N3, PS-N3, and PCL-N3) and ethynylfunctional CA under ambient conditions, yielding CA endfunctional polymers (mPEG-Cholic, PMMA-Cholic, PS-Cholic, and PCL-Cholic). Finally, the obtained CA end-capped polymers were employed as the macroinitiators in the ROP of ecaprolactone (ε-CL) yielding AB3-type miktoarm star polymers (mPEG-Cholic-PCL3, PMMA-Cholic-PCL3, and PS-Cholic-PCL3) and asymmetric star polymer [Cholic-(PCL)4]. The chemical structures of the obtained intermediates and polymers were confirmed via Fourier transform infrared and 1H nuclear magnetic resonance spectroscopic techniques. Thermal decomposition behaviors and phase transitions were studied in detail using thermogravimetric analysis and differential scanning calorimetry experiments.
Click grafting of alkyne-containing vinyl polymers onto biosynthesized extracellular matrix protein containing azide functionality and adhesion control of human umbilical vein endothelial cells
Yamada, Tomoki,Takasu, Akinori
, p. 41445 - 41456 (2015)
In vivo incorporation of a phenylalanine (Phe) analogue, p-azidophenylalanine (p-N3Phe) into an artificial extracellular matrix protein (aECM-CS5-ELF) was accomplished using a bacterial expression host that harbors the mutant phenylalanyl-tRNA synthetase (PheRS) with an enlarged binding pocket, in which the Ala294Gly/Thr251Gly mutant PheRS (PheRS) was expressed under the control of T7 promoters. In this study, biosynthesized aECM-CS5-ELF containing p-N3Phe (aECM-CS5-ELF-N3) was coupled with alkyne-containing vinyl polymers prepared via controlled radical polymerization of three vinyl monomers, (styrene, acrylamide, and N-isopropylacrylamide) using a trithiocarbonate as the RAFT agent. Grafting of the vinyl polymers onto the aECM was accomplished via a copper-catalyzed alkyne-azide click reaction. The lower critical transition temperature (LCST) was evaluated, as well as the solubility in aqueous and organic media, which are dependent on the incorporation ratio of p-N3Phe and species of graft chains, in which the LCST behavior was altered remarkably when poly(N-isopropylacrylamide) moieties were attached as side chains. Circular dichroism measurements indicate conformational change was not induced by the grafting. Specific adhesion of human umbilical vein endothelial cells (HUVECs) onto the (aECM-CS5-ELF-N3)-graft-poly(N-isopropylacrylamide) composite surface and subsequent temperature-sensitive detachment were also demonstrated.
Amphiphilic Modulation of Glycosylated Antitumor Ether Lipids Results in a Potent Triamino Scaffold against Epithelial Cancer Cell Lines and BT474 Cancer Stem Cells
Idowu, Temilolu,Samadder, Pranati,Arthur, Gilbert,Schweizer, Frank
, p. 9724 - 9738 (2017)
The problems of resistance to apoptosis-inducing drugs, recurrence, and metastases that have bedeviled cancer treatment have been attributed to the presence of cancer stem cells (CSCs) in tumors, and there is currently no clinically indicated drug for their eradication. We previously reported that glycosylated antitumor ether lipids (GAELs) display potent activity against CSCs. Here, we show that by carefully modulating the amphiphilic nature of a monoamine-based GAEL, we can generate a potent triamino scaffold that is active against a panel of hard-to-kill epithelial cancer cell lines (including triple-negative breast) and BT474 CSCs. The most active compound of this set, which acts via a nonmembranolytic, nonapoptotic caspase-independent mechanism, is more effective than cisplatin and doxorubicin against these cell lines and more potent than salinomycin against BT474 CSCs. Understanding the combination of factors crucial for the enhanced cytotoxicity of GAELs opens new avenues to develop potent compounds against drug-resistant cancer cells and CSCs.
Synthesis and micellar behavior of novel amphiphilic poly[bis(trifluoroethoxy)phosphazene]- co -poly[(dimethylamino)ethyl methacrylate] block copolymers
Tian, Zhicheng,Liu, Xiao,Chen, Chen,Allcock, Harry R.
, p. 2502 - 2508 (2012)
A number of amphiphilic diblock copolymers based on poly[bis(trifluoroethoxy)phosphazene] (TFE) as the hydrophobic block and poly[(dimethylamino)ethyl methacrylate] (PDMAEMA) as the hydrophilic block were developed. The TFE block was synthesized first by the controlled living cationic polymerization of a phosphoranimine, followed by replacement of all the chlorine atoms using sodium trifluoroethoxide. To allow for the growth of the PDMAEMA block, 3-azidopropyl-2-bromo-2-methylpropanoate, an atom transfer radical polymerization (ATRP) initiator, was grafted onto the end-cap of the TFE block via the "click" reaction followed by the ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Once synthesized, micelles were formed by a standard method, and their characteristics were examined using fluorescence techniques, dynamic light scattering, and transmission electron microscopy. The critical micelle concentrations of the diblock copolymers as determined by fluorescence techniques using pyrene as a hydrophobic probe were between 3.47 and 9.55 mg/L, with the partition equilibrium constant of pyrene in these micelles ranging from 0.12 × 105 to 1.52 × 10 5. The diameters measured by dynamic light scattering were 100-142 nm at 25 °C with a narrow distribution, which were also confirmed by transmission electron microscopy.
Thermal responsiveness and binding affinity of cucurbit[7]uril terminal poly(: N -isopropylacrylamide)
Hou, Shengzhen,Chen, Hao,Qiu, Xiumin,Xu, Wenchao,Tan, Yebang
, p. 14831 - 14834 (2017)
We synthesized cucurbit[7]uril terminal poly(N-isopropylacrylamide) (CB[7]-PNIPAM) via a click reaction of monopropargylated CB[7] and azido terminal PNIPAM. We found that the introduction of CB[7] and charged guest molecules raised the lower critical solution temperature of PNIPAM significantly and CB[7]-PNIPAM maintained high binding affinity of CB[7].
Highly efficient "click" functionalization of poly(3-azidopropyl methacrylate) prepared by ATRP
Sumerlin, Brent S.,Tsarevsky, Nicolay V.,Louche, Guillaume,Lee, Robert Y.,Matyjaszewski, Krzysztof
, p. 7540 - 7545 (2005)
To prepare polymers with pendant functionality capable of participating in highly efficient CuI-catalyzed 1,3-dipolar cycloaddition of azide and alkynes, monomers with acetylene or azido groups were polymerized via controlled radical polymerization. Atom transfer radical polymerization (ATRP) of propargyl methacrylate (PgMA) resulted in high polydispersities (M w/Mn > 3), multimodal molecular weight distributions, and cross-linked networks at moderate to high conversion. The poor results obtained with this monomer were presumably due to addition of the propagating radicals to the acetylene group, transfer reactions, and/or interference with the catalyst. A novel monomer, 3-azidopropyl methacrylate (AzPMA), was polymerized via ATRP with good control of the polymer molecular weight distribution and retention of chain functionality. Poly(3-azidopropyl methacrylate) was coupled with propargyl alcohol, propargyl triphenylphosphonium bromide, propargyl 2-bromoisobutyrate, and 4-pentynoic acid via a highly efficient "click" reaction in the presence of a CuI catalyst. The azido-functionalized polymer demonstrated enhanced reactivity as compared to small molecules with comparable structures. The ability of the coupling reactions to be conducted at room temperature without significant excess of reagents makes this an attractive alternative to preparing (co)polymers with high degrees of functionalization.
Photodynamic therapy via FRET following bioorthogonal click reaction in cancer cells
Bio, Moses,Rajaputra, Pallavi,You, Youngjae
, p. 145 - 148 (2016)
Longer wavelength light (650-800 nm) is desired to treat large tumors in photodynamic therapy (PDT). However, shorter wavelength light is needed in PDT for thin tumors, not to cause undesirable local side effects. We proposed a strategy for stepwise optical imaging and PDT using a bioorthogonal click chemistry and fluorescence resonance energy transfer (FRET). We prepared azidyl rhodamine (Rh-N3, clickable FD) and cyclooctynyl phthalocyanine [Pc-(DIBAC), clickable PS], with which, here, we demonstrate that the non-catalytic click chemistry is rapid and efficient in cancer cells and FRET from a fluorescence dye (FD) to a photosensitizer (PS) is sufficient to generate enough singlet oxygen killing cancer cells by using shorter wavelength light.
Self-assembly of fullerene-based janus particles in solution: Effects of molecular architecture and solvent
Lin, Zhiwei,Lu, Pengtao,Hsu, Chih-Hao,Yue, Kan,Dong, Xue-Hui,Liu, Hao,Guo, Kai,Wesdemiotis, Chrys,Zhang, Wen-Bin,Yu, Xinfei,Cheng, Stephen Z. D.
, p. 11630 - 11635 (2014)
Two molecular Janus particles based on amphiphilic [60]fullerene (C 60) derivatives were designed and synthesized by using the regioselective Bingel-Hirsh reaction and the click reaction. These particles contain carboxylic acid functional groups, a hydrophilic fullerene (AC 60), and a hydrophobic C60 in different ratios and have distinct molecular architectures: 1:1 (AC60-C60) and 1:2 (AC60-2C60). These molecular Janus particles can self-assemble in solution to form aggregates with various types of micellar morphology. Whereas vesicular morphology was observed for both AC 60-C60 and AC60-2C60 in tetrahydrofuran, in a mixture of N,N-dimethylformamide (DMF)/water, spherical micelles and cylindrical micelles were observed for AC60-C 60 and AC60-2C60, respectively. A mechanism of formation was tentatively proposed based on the effects of molecular architecture and solvent polarity on self-assembly.
Amphiphilic triblock copolymer bioconjugates with biotin groups at the junction points: Synthesis, self-assembly, and bioactivity
Jin, Jie,Wu, Dongxia,Sun, Pingchuan,Liu, Li,Zhao, Hanying
, p. 2016 - 2024 (2011)
Poly(ε-caprolactone)-block-poly(ethylene glycol)-block-poly(ε- caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers with biotin groups at the junction points were synthesized based on a combination of click chemistry and ring-opening polymerization (ROP). Alkyne-functionalized PCL-b-PEG-b-PCL triblock copolymers were synthesized by using alkyne-functionalized PEG as macroinitiators in ROP of ε-caprolactone. Click chemistry was employed in the synthesis of the biotinylated triblock copolymers. Gel permeation chromatography and 1H NMR results all indicated successful synthesis of well-defined triblock copolymers. The triblock copolymer chains can self-assemble into micelles in aqueous solution. The PCL blocks form the cores of the micelles and the hydrophilic PEG blocks form the coronae. The biotin moieties distribute at the interface of the micelles. Upon addition of avidin to the micellar solution, micelles aggregated together forming micellar aggregates due to the interaction between avidin and biotin. The avidin/HABA competitive binding assay also proved the bioavailability of the biotinylated micelles to avidin.
Fluorescent and Water Dispersible Single-Chain Nanoparticles: Core–Shell Structured Compartmentation
Hoffmann, Justus F.,Roos, Andreas H.,Schmitt, Franz-Josef,Hinderberger, Dariush,Binder, Wolfgang H.
supporting information, p. 7820 - 7827 (2021/03/01)
Single-chain nanoparticles (SCNPs) are highly versatile structures resembling proteins, able to function as catalysts or biomedical delivery systems. Based on their synthesis by single-chain collapse into nanoparticular systems, their internal structure is complex, resulting in nanosized domains preformed during the crosslinking process. In this study we present proof of such nanocompartments within SCNPs via a combination of electron paramagnetic resonance (EPR) and fluorescence spectroscopy. A novel strategy to encapsulate labels within these water dispersible SCNPs with hydrodynamic radii of ≈5 nm is presented, based on amphiphilic polymers with additional covalently bound labels, attached via the copper catalyzed azide/alkyne “click” reaction (CuAAC). A detailed profile of the interior of the SCNPs and the labels’ microenvironment was obtained via electron paramagnetic resonance (EPR) experiments, followed by an assessment of their photophysical properties.
ATP13A3 is a major component of the enigmatic mammalian polyamine transport system
Hamouda, Norin Nabil,van den Haute, Chris,Vanhoutte, Roeland,Sannerud, Ragna,Azfar, Mujahid,Mayer, Rupert,Calabuig, álvaro Cortés,Swinnen, Johannes V.,Agostinis, Patrizia,Baekelandt, Veerle,Annaert, Wim,Impens, Francis,Verhelst, Steven H.L.,Eggermont, Jan,Martin, Shaun,Vangheluwe, Peter
, (2021/03/24)
Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG.
