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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Novel dual ROS-sensitive and CD44 receptor targeting nanomicelles based on oligomeric hyaluronic acid for the efficient therapy of atherosclerosis

Xiaoya Hou,Hua Lin,Xiudi Zhou,Ziting Cheng,Yi Li,Xue Liu,Feng Zhao,Yanping Zhu,Peng Zhang,Daquan Chen

Although the clinical usage of drugs administration was raising, the application of nanoparticles encapsulating the hydrophobic drugs with plummy efficiency was very scarce for atherosclerosis (AS) treatment. In this work, a novel dual ROS-sensitive and CD44 receptors targeting amphiphilic carrier material, oligomeric hyaluronic acid-2′-[propane-2,2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (oHA-TKL-Fc), named HASF, was synthesized and characterized by 1 H-NMR spectra. Then, we combined curcumin (Cur) with HASF into nano-micelles ( [email protected] micelles) by self-assembling method. The resulting [email protected] micelles had the average size of 150.8 nm and zeta potential of -35.04 mV to maintain the will-defined spheroidal structure and stability. Importantly, the [email protected] micelles had ultrahigh entrapment efficiency (about 51.41 %). Moreover, in vitro release study, Cur release from [email protected] micelles was effective in the reactive oxygen species (ROS) condition, and the release rate was interrelated with the concentration of hydrogen peroxide (H 2 O 2 ). Further, fluorescence imaging showed that the [email protected] micelles could more selective access to Raw 264.7 cells than free Cur via oHA-receptor mediated endocytosis. The MTT assay attested the safety of amphiphilic carrier material HASF. Additionally, the results of in vivo Oil red O lipid staining studies showed that the lesion area of the aorta was reduced to 47.3±3.4 % with [email protected] micelles, compared with the lesion area of Cur group (63.2±2.7 %), [email protected] micelles had the more remarkable effect in reducing lesion area (*P < 0.05). Consequently, the novel dual ROS-sensitive and CD44 receptors targeting drug delivery system would become a promising strategy for atherosclerosis.

CAS / MDL: 7722-84-1
研究领域: 药学 · 纳米技术 · 心血管疾病
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Carbohydrate Polymer Technologies and Applications · 2023 · IF 5.5

Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug

Zi-Dan Wang,Hu-Hong Peng,Dong-Qiang Lin,Yi-Xin Guan

Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H 2 O 2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.

CAS / MDL: 7244-02-2
研究领域: 药学 · 癌症研究 · 纳米技术 · 药物递送系统
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JOURNAL OF APPLIED POLYMER SCIENCE · 2024 · IF 2.7

ROS-sensitive selenium-containing cationic brush polymer with potent gene transfection efficiency and biocompatibility

Yonghua Zhai,Lili Wu,Jie Gao,Jingsheng Zhou,Longhai Du,Xiaoda Fu,Yang Gao,Tinglin Zhang,Mengya Zhang,Weihong Lu,Yan Wu

Smart gene delivery vectors are gaining increasing attention in gene therapy, owing to their low cytotoxicity and intrinsic responsiveness. Our previously fabricated novel cationic brush polymer, comprising C  Se bonds and tertiary amine EGIn- g -PDMAEMA, shows potential for gene transfection. In this study, its high efficiency for siRNA/pDNA transfection and low cytotoxicity in reactive oxygen species (ROS)-rich microenvironments is substantiated in vitro. Its superior binding capacity with siRNA/pDNA is confirmed by agarose gel electrophoresis assay. The threshold weight ratios for siRNA/pDNA migration delay are 15 and 3 (polymer-to-nucleic acid, w/w), respectively. Fluorescence microscopy and ribonucleotide reductase regulatory subunit M2 gene silencing essay verify the biodegradability and responsive control release of nucleic acids under hydrogen peroxide stimulation in Huh-7 cells. Compared with the gold standard, polyethylenimine 25 kDa, the target polymer displays superior transfection efficiency in ROS-rich tumor cells under serum-free conditions. Furthermore, the vector–nucleic acid complexes exhibit over 90% cell viability at a high concentration of 12 μg mL −1 and good colloidal stability in phosphate-buffered saline (PBS) and 10% fetal bovine serum-PBS for 24 h. The efficient control release and expression of nucleic acids in ROS environments and reduced cytotoxicity highlight the superiority of EGIn- g -PDMAEMA as a gene delivery platform for tumor gene therapy.

研究领域: 生物医学工程 · 基因治疗 · 材料科学 · 分子生物学
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