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BIOMEDICINE & PHARMACOTHERAPY · 2024 · IF 6.9

Design and synthesis of nucleotidyl lipids and their application in the targeted delivery of siG12D for pancreatic cancer therapy

Yufei Pan,Yuejie Zhu,Yuan Ma,Jiamei Hong,Wenting Zhao,Yujing Gao,Jing Guan,Runan Ren,Qi Zhang,Jing Yu,Zhu Guan,Zhenjun Yang

Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.

研究领域: 药学 · 癌症治疗 · 纳米技术 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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WATER SCIENCE AND TECHNOLOGY · 2019 ·Vol. 79 ·期 11 ·2068-2078 · IF 1.624

Enhanced permeability and fouling-resistant capacity of poly(vinylidene fluoride) ultrafiltration membrane based on the PPG-co-PEG-co-PPG copolymer with two hydrophobic terminals and one hydrophilic intermediate

Zhang Bo,Wang Panpan,Yu Jianxin,Jiang Haicheng,Gao Po,Ma Jun

A simple and efficient route was used to prepare an amphiphilic copolymer (poly(propylene glycol)-co-poly(ethylene glycol)-co-poly(propylene glycol)) (PPG-co-PEG-co-PPG) by one-pot polymerization reaction. This copolymer was used as the hydrophilic additive in preparation of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes via immersion–precipitation process. Surface characteristics of the membranes were confirmed by contact angle measurements, zeta potential, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. During filtration experiments, the modified membranes showed better permeation and antifouling performances compared to PVDF membranes with bovine serum albumin, sodium alginate and yeast. After hydraulic stirring cleaning with deionized water, water flux recovery and rejection ratio of the modified membranes were higher than those of pristine PVDF membrane, and the flux recovery ratio was maximized at 94.29%. It was suggested that PPG-co-PEG-co-PPG copolymer was anchored in the PVDF membrane through the two hydrophobic ends of PPG blocks, while the hydrophilic intermediate of the PEG block segregated onto the membrane or pore surface during the membrane preparation process. The synthesized method of amphiphilic PPG-co-PEG-co-PPG copolymer paved a novel way to solve the problems of less compatibility between the copolymer and membrane matrix and instability with water molecules in the ultrafiltration process.

研究领域: 材料科学 · 高分子科学 · 膜技术 · 环境工程 · 化学工程
✓ 已验证 DOI 高影响因子
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ANALYTICAL LETTERS · 2026 · IF 1.8

Fluorescent Hydrogel Sensor Based upon Polyvinyl Alcohol (PVA), Polyethylene Glycol (PEG), and Aptamer-Functionalized Graphene Quantum Dots (GQDs-Apt) for the On-Site Determination of Acetamiprid Residues in Vegetables

Xin Zhang,Jingcheng Huang,Rui Xu,Jiashuai Sun,Pengwei Zhang,Xingkang Zhang,Fangling Du,Yemin Guo,Xia Sun

There is a growing concern that residues of agricultural chemicals in fresh produce may pose a risk to public health. Acetamiprid, a broad spectrum insecticide, has attracted increasing attention due to its potential toxicity and environmental persistence. Although conventional analytical techniques offer high accuracy, they are often labor intensive and instrument dependent. To address these limitations, this study aimed to develop a rapid, sensitive, and straightforward method for the detection of acetamiprid residues in leafy vegetables. This study was the first to utilize the water retention property of hydrogels in the detection reaction. The assay could be conducted directly on the vegetable surface without spraying detection reagents. This design greatly simplified the analytical procedure. A fluorescent aptamer based composite hydrogel sensor was successfully fabricated using polyvinyl alcohol (PVA), a polyethylene glycol (PEG) based crosslinked polymer, and aptamer functionalized graphene quantum dots (GQDs-Apt). The composite hydrogel was crosslinked with glutaraldehyde (GA), resulting in a stable three-dimensional network structure with excellent biocompatibility and mechanical strength. The GQDs-Apt conjugates served as the signal reporting units, whose fluorescence characteristics were modulated by the binding interaction between the aptamer and acetamiprid, thereby conferring high sensitivity and selectivity. In the absence of acetamiprid, the aptamer probe remained associated with the graphene quantum dot surface, leading to fluorescence quenching. Upon introduction of the target pesticide, the aptamer preferentially bound to acetamiprid, inducing a conformational change that facilitated detachment of the probe from the quantum dot surface and subsequent fluorescence recovery. This "quenching–recovery" signaling mechanism provided the theoretical basis and practical framework for the quantitative detection of acetamiprid. The fluorescence changes within the hydrogel network were exploited for both the screening and precise quantification of the pesticide. Performance metrics revealed a limit of detection (LOD) of 0.005 μmol L−1, a dynamic range of 0.01 to 10 μmol L−1, and R2 of 0.9971. Validation in real matrices of cabbage, leek and tomato demonstrated robust accuracy and repeatability, with fortified recoveries between 96.11% and 99.47%, relative standard deviation (RSD) below 3.11%, and an equilibration time of less than 20 minutes. This strategy provides a rapid, user friendly, high resolution, and reliable tool for agricultural product safety and environmental monitoring.

✓ 已验证 DOI 高影响因子
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JOURNAL OF MOLECULAR LIQUIDS · 2022 · IF 6.633

Enhancement of long alkyl-chained imidazolium ionic liquids for the formation and extraction behaviour of PEG 600/(NH4)2SO4 aqueous two-phase system by complexing with Triton X-100

Yanrong Cheng,Xia Guo,Delan Ge,Wenlin Xu,Yaqiong Wang

Broadening the polarity range of polymer-based aqueous two-phase systems (ATPSs) is of practical significance. Recently, ionic liquids have been used as adjuvants to modify the polarity and properties of PEG-rich phases in PEG/salt ATPSs. However, thus far, only short alkyl (containing less than 8 carbon atoms)-chained ionic liquids have been able to promote the extraction performance of ATPSs; long alkyl-chained ionic liquids have decreased the extraction performance significantly due to their distribution in the bottom phase. In the present study, we found that by complexing with Triton X-100 (TX-100), long alkyl-chained imidazolium ionic liquids [C n mim]Br (n = 10 and 12) as adjuvants were enriched in the top phase of PEG/salt ATPSs, and hence, the polarity difference of the two phases were increased. By extracting two model substances (S-mandelic acid (MA) and l -tryptophan (Trp)), it was concluded that, although the long alkyl-chained [C n mim]Br adjuvant decreased the extraction performance of the ATPS substantially, the long alkyl-chained [C n mim]Br/TX-100 complex as the adjuvant enhanced the extraction performance of the ATPS significantly. Compared with the case without an adjuvant, when the [C 12 mim]Br/TX-100 complex and the [C 10 mim]Br/TX-100 complex were used as the adjuvants, the partition coefficients of MA and Trp in the PEG 600/(NH 4 ) 2 SO 4 ATPS were increased up to 3 ∼ 4 times, much better than those with short alkyl-chained ionic liquid as the adjuvant. Moreover, the [C 12 mim]Br/TX-100 complex is more conductive to the transfer of MA into the PEG-rich phase, and the [C 10 mim]Br/TX-100 complex is more conductive to the transfer of Trp into the PEG-rich phase.

CAS / MDL: 85100-78-3 25322-68-3
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ACS Omega · 2019 · IF 2.584

Enhanced Rheological Properties of PLLA with a Purpose-Designed PDLA-b-PEG-b-PDLA Triblock Copolymer and the Application in the Film Blowing Process to Acquire Biodegradable PLLA Films

Yuanping Jiang,Cong Yan,Dawei Shi,Zhengying Liu,Mingbo Yang

The inadequate rheological properties limit the film blowing process of biodegradable polylactic acid (PLA), thus hindering its potential application in environmentally friendly packaging films and mulch films. Herein, biodegradable polyethylene glycol (PEG) and d-lactide were used to synthesize three kinds of poly-d-lactic acid (PDLA)-b-PEG-b-PDLA (DPD) triblock copolymers, and their effects on stereocomplex (sc) structure formation and rheological properties of the composites were studied. The results showed that the poly l-lactic acid (PLLA)/DPD4k sample introduced the highest sc content, storage modulus, and complex viscosity value compared with PLLA/DPD2k and PLLA/DPD10k at the same loading condition, indicating that the PEG4k chains can better accelerate the formation of a sc network between DPD4k and the PLLA matrix. The introduction of 10 wt % DPD4k also resulted in about 38 times longer relaxation time and a strain-hardening behavior during the steady biaxial extension of PLLA. At last, the continuous film blowing process was successfully conducted in the PLLA/DPD4k composites, which acquired a stable blow-up ratio of 3.07. On the basis of the above results, the soft chain-grafted PDLA copolymer may provide a novel method for film blowing of biodegradable PLA.

CAS / MDL: 25322-68-3 9002-93-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2019 · IF 2.983

Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation

Jinsheng Lin,Tianpei Huang,Mengxue Feng,Dan Li,Danna Zhao,Jichao Wang,Jianyang Jin,Wenquan Zhu,Min Li

During the related substances testing of mirabegron extended release tablets, an unknown peak was observed in HPLC chromatograms in a level exceeding the identification threshold. By using a strategy that combines LC–PDA/UV-MS n with mechanism-based stress studies, the unknown peak was rapidly identified as cyanomethyl mirabegron, a solution degradant that is caused by a Strecker-like reaction between the API, formaldehyde (an impurity in PEG), and HCN (an impurity in HPLC grade acetonitrile). The mechanism of the solution degradation chemistry was verified by stressing mirabegron with formaldehyde and trimethylsilyl cyanide (TMSCN, a synthetic reagent that generates HCN upon contact with water), in which the secondary amine group of mirabegron first reacts with formaldehyde to form the iminium ion intermediate; the latter then undergoes a nucleophilic attack by cyanide to yield the cyanomethyl mirabegron. The structure of the impurity was further confirmed through the synthesis of the impurity and subsequent structure characterization by 1D and 2D NMR. Due to the ubiquitous presence of formaldehyde in pharmaceutical excipients (e.g., PEG and polysorbate) and trace amount of HCN in HPLC grade acetonitrile, this type of solution degradation would likely occur in sample preparations of pharmaceutical finished products containing APIs with primary and secondary amine moieties. In a GMP environment, such an event may trigger undesirable out-of-specification (OOS) investigations; the results of this paper should help resolve such OOS investigations or even prevent these events from happening in the first place.

CAS / MDL: 7677-24-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SEPARATION AND PURIFICATION TECHNOLOGY · 2024 · IF 8.1

Evaluation of chiral dehydroabietic acid-terminated tetra-arm PEG as an assisted phase-forming polymer and chiral selector for the enantioseparation of propranolol racemate in aqueous two-phase systems

Qinghui Liang,Li Ge,Qiang Lu,Gang Hu,Kedi Yang

In this work, we successfully synthesized a chiral dehydroabietic acid-terminated tetra-arm PEG (4-arm PEG-DHAA) and utilized it to construct a chiral aqueous two-phase system (ATPS) alongside PEG2000 and (NH 4 ) 2 SO 4 . The 4-arm PEG-DHAA served as both an assisted phase-forming polymer and a chiral selector. This ATPS can be employed for chiral recognition and liquid–liquid enantioselective extraction of the propranolol enantiomers. The effects of four primary factors, namely initial r ac-propranolol concentration, extraction temperature, system pH, and the concentration of 4-arm PEG-DHAA on enantioseparation, were thoroughly evaluated. Furthermore, the optimization of extraction conditions was conducted using the response surface methodology. The results indicated that the chiral ATPS has better and higher enantioselectivity, with a one-step chiral extraction achieving an e.e. up to 57% and a yield exceeding 73% for S-isomers under the optimized conditions. In addition, the chiral ATPS can be regenerated through simple back-extraction with diethyl ether and reused at least five times, achieving similar enantioselective extraction results. This research presents a valuable enantioseparation approach for propranolol enantiomers via liquid–liquid enantioselective extraction using the chiral ATPS.

CAS / MDL: 25322-68-3 525-66-6
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Acidity-Triggered Tumor-Targeted Nanosystem for Synergistic Therapy via a Cascade of ROS Generation and NO Release

Yufei Cao,Mingsheng Liu,Ju Cheng,Juanjuan Yin,Congshu Huang,Haiyan Cui,Xiangdong Zhang,Guanghui Zhao

Nitric oxide (NO) gas therapy has aroused intense interest in recent years. l-Arginine (l-Arg) reacts with reactive oxygen species (ROS) in tumor cells to generate NO. This phenomenon represents an effective method for tumor therapy. However, endogenous ROS levels in most types of tumor cells cannot enable an effective reaction. β-Lapachone is generally used to increase H2O2, which can oxidize guanidine derivatives to form nitric oxide in tumor cells. In addition, based on the ferrocene (Fc)-catalyzed Fenton reaction, ·OH is generated from H2O2, and the ONOO– could be generated from an interaction between ·O2– (generated through the Haber–Weiss reaction) and NO. Arg-rich poly(ε-caprolactone) (PCL)-b-PArg, a macromolecular NO donor, was accurately synthesized to avoid premature l-Arg leakage during in vivo transport. In this design, the self-assembled PCL-b-PArg nanoparticles were dressed with the tumor-shreddable masking (PEG-b-PDMA, a negatively charged pH-sensitive hydrophilic diblock polymer), to prepare P-lapa-Fc nanoparticles and hide penetrative capability in the circulation. The experimental results confirmed that this synergistic therapy based on ROS and NO had a significant inhibitory effect on cancer cells, thereby providing new inspiration for NO gas treatment.

研究领域: 癌症治疗 · 纳米医学 · 药物化学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 1 ·1-10 · IF 5.479

CdSe/ZnS quantum dots coated with carboxy-PEG and modified with the terbium(III) complex of guanosine 5′-monophosphate as a fluorescent nanoprobe for ratiometric determination of arsenate via its inhibition of acid phosphatase activity

Wen Shao-Hua,Liang Ru-Ping,Zeng Hui-Hui,Zhang Li,Qiu Jian-Ding

A ratiometric fluorometric method is described for the determination of arsenate via its inhibitory effect on the activity of the enzyme acid phosphatase. A nanoprobe was designed that consists of CdSe/ZnS quantum dots (QDs) coated with the terbium(III) complex of guanosine monophosphate (Tb-GMP). The nanoprobe was synthesized from carboxylated QDs, Tb(III) and GMP via binding of Tb(III) by both the carboxy and the phosphate groups. The nanoprobe, under single-wavelength excitation (at 280 nm), displays dual (red and green) emission, with peaks at around 652 nm from the QDs, and at 547 nm from the Tb-GMP coordination polymers. It is shown to be a viable nanoprobe for fluorometric determination of As(V) detection through it inhibitory action on the activity of acid phosphatase (ACP). The enzyme destroys the Tb-GMP structure via hydrolysis of GMP, and hence the fluorescence of the Tb-GMP complex is quenched. In contrast, the fluorescence of the CdSe/ZnS QDs remains inert to ACP. It therefore can serve as an internal reference signal. In the presence of arsenate (an analog of phosphate), the activity of ACP is inhibited due to competitive binding. Thus, hydrolysis of GMP is prevented. These findings were used to design a ratiometric fluorometric method for the quantification of As(V). The ratio of fluorescences at 547 and 652 nm increases linearly in the 0.5 to 200 ppb As(V) concentation range, and the limit of detection is 0.39 ppb. Under a UV lamp, the probe shows distinguishable color from green to red on increasing the concentration of As(V). Schematic illustration of CdSe/ZnS quantum dot coated with carboxy-PEG and modified with the terbium(III)-GMP complex as a fluorescent nanoprobe for ratiometric determination of arsenate via its inhibition of ACP activity.

CAS / MDL: 13451-19-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN POLYMER JOURNAL · 2013 · IF 2.562

Multiresponsive supramolecular gels constructed by orthogonal metal–ligand coordination and hydrogen bonding

Wengui Weng,Xiuli Fang,Huan Zhang,Huiying Peng,Yangju Lin,Yinjun Chen

Macromonomers bearing tridentate 2,6-bis(1,2,3-trizol-4-yl)pyridine (BTP) ligand unit synthesized via CuAAC “click” chemistry in the middle of the chain and two ureidopyrimidinone (UPy) motifs on the ends linked to the central BTP unit via PEGs of various lengths were synthesized and used for the study of gelation both with and without the presence of Eu(III) ions. Various interesting gelation behaviors were found. Gels exhibited various multi-responsive properties, including photoluminescence, mechanoresponsive properties, self-healing abilities, thermorepsonsive properties and chemoresponsive properties. The different gelation abilities and multi-responsive properties for different systems were shown to be resulted from difference in PEG linker lengths and the introduction of orthogonal metal–ligand coordination and hydrogen bonding interactions. The selective responsiveness to different chemicals would allow the development of modular sensory systems that utilize a combination of orthogonal supramolecular interactions.

研究领域: 超分子化学 · 材料科学 · 高分子化学
✓ 已验证 DOI 高影响因子
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ACS Applied Materials & Interfaces · 2013 · IF 5.008

Reduction-Cleavable Polymeric Vesicles with Efficient Glutathione-Mediated Drug Release Behavior for Reversing Drug Resistance

Tianbin Ren,Wei Wu,Menghong Jia,Haiqing Dong,Yongyong Li,Zhouluo Ou

In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance. Polymeric vesicles were self-assembled from triblock copolymers with disulfide-bond-linked poly(ethylene glycol) (PEG) and poly(ε-benzyloxycarbonyl-l-lysine) (PzLL). Observations from transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline an obvious hollow structure surrounded by a thin outer layer, indicating the successful formation of the vesicles. Using fluorescently detectable doxorubicin hydrochloride (DOX·HCl) as the model drug, a significant acceleration of drug release regulated by glutathione (GSH) was found (>3-fold difference). Upon incubation of the DOX·HCl-loaded polymeric vesicles with the HeLa cervical cancer cell line exposed to glutathione, an enhanced nuclear accumulation of DOX·HCl was observed, elicited by the preferred disassembly of the vesicle structure under reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC·HCl)-resistant breast cancer cell line MDA-MB-231, it was found that cell viability was significantly reduced after treatment with GC·HCl-loaded polymeric vesicles, indicating that these vesicles can help to reverse the drug resistance.

研究领域: 药理学 · 癌症研究 · 聚合物化学 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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Polymer Chemistry · 2024 · IF 4.1

Facile synthesis of asymmetric molecular brushes with triple side chains using a multivalent monomer strategy

Shiya Cao,Wenyi Liu,Bicai Yang,Yuan Zheng,Shaoliang Lin,Binbin Xu

Heterografted molecular brushes (HMBs) bearing two or more types of side chains have attracted tremendous attention because of their asymmetric structures and multiple functionalities. However, the controlled synthesis of HMBs with three types of side chains remains a challenge. The structure–property–application correlations of HMBs with three types of side chains are still not clear. Herein, based on the multivalent monomer strategy, we report the synthesis of well-defined asymmetric HMBs comprising three different side chains by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization, atom transfer radical polymerization (ATRP), thiol–epoxy coupling reaction, and ring-opening polymerization (ROP). PA-g-PAzo/PEG/PLA with a polyacrylate (PA) backbone, hydrophobic poly(azobenzene-methacrylate) (PAzo) brush, hydrophilic polyethylene glycol (PEG) brush, and hydrophobic polylactide (PLA) brush was synthesized and characterized. The self-assembly behavior of PA-g-PAzo/PEG/PLA with a short backbone and relatively strong intermolecular association in solutions was investigated. Well-defined platelets with tunable morphologies were constructed. Subsequently, PA-g-PFA/PEG/PLA with a fluorophilic poly(pentafluoropropyl acrylate) (PFA) brush, hydrophilic PEG brush, and lipophilic PLA brush was synthesized and further used as an efficient surfactant for the stabilization of different emulsions. Our study offers a platform for exploring the unique properties of asymmetric HMBs.

研究领域: 高分子化学 · 材料科学 · 纳米技术 · 胶体科学
✓ 已验证 DOI 高影响因子
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