Advanced Healthcare Materials
·
2023
·
IF 10
Ye Yuan,Chunyu Tian,Qi Wang,Xinyu Qiu,Yufang Wang,Hulin Jiang,Jifu Hao,Yujing He
As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H 2 O 2 or relatively high pH value for Fenton reaction-dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid-based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction-independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG 2K -DSPE-modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe 2+ , and subsequently the formed iron redox pair (Fe 2+ /Fe 3+ ) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction-independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor-killing ability with negligible side effect. Consequently, this two-pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy.
研究领域:
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 46
·6418-6426
·
IF 0
Wenyu Li,Peng Zhang,Kun Zheng,Qiaoling Hu,Youxiang Wang
Extracellular stability to protect DNA against nucleases and stimulus-triggered intracellular DNA release are key factors in designing non-viral gene vectors. In this study, the diselenide-linked polycation mPEG–SeSe–PEI was developed as a new type of PEG-detachable gene vector for redox-responsive gene delivery. The corresponding stable analog mPEG–PEI and the disulfide-linked polycation mPEG–SS–PEI were synthesized as controls. The results showed that all the PEGylated polycations could condense DNA into tightly packed spherical nanoparticles about 80 nm in size, which showed excellent stability under physiological conditions. The results of zeta-potential measurements, stability tests and DNA release ability assay indicated that at a GSH concentration of 0.3 mM, the diselenide bonds were more easily cleaved than disulfide bonds, which facilitated dePEGylation and DNA release. Meanwhile, it was interestingly found that mPEG–SeSe–PEI/DNA polyplexes showed higher gene expression than mPEG–SS–PEI/DNA polyplexes in both HEK293T and HepG2 cells. Confocal laser scanning microscope (CLSM) images revealed that mPEG–SeSe–PEI/DNA polyplexes showed more efficient endosomal escape ability than mPEG–SS–PEI/DNA polyplexes. Based on these results, the diselenide bonds as a novel strategy are more suitable to address the challenging problem of extracellular stability and intracellular DNA release.
研究领域:
基因递送
·
聚合物化学
·
分子生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Ruyi Zhou,Hongxia Tian,Yu Xue,Wen Lv,Mingye Zhu,Jiangang Li,Shujuan Liu,Qiang Zhao
Developing an innovative phototherapy agent that integrates tumor diagnosis and treatment functions is crucial for improving the precision and efficacy of anti-tumor treatment. Traditional aza-dipyrromethene (aza-DP) dyes exhibited strong photothermal effects, high molar absorption coefficients, and good photostability, but their photodynamic effects were weak. Metal elements were introduced into the aza-DP structure to address this issue, thereby enhancing inter-system crossing (ISC) and improving the photodynamic effect. In this study, a series of Zn(II)-chelated aza-DP complexes were designed and synthesized as novel phototherapy agents. To further extend the absorption wavelength of aza-DP in the near-infrared region, strong electron-donating groups of N,N-dimethylaniline were introduced at the 1,7 positions for modification, and both photodynamic and photothermal effects were also improved. The nanoparticles prepared by coating the phototherapy agents as mentioned above with amphiphilic DSPE-mPEG 5000 exhibit excellent hydrophilicity and photostability. Under 660 nm laser irradiation, the nanoparticles exhibited good synergistic therapeutic effects in vivo , with significant anti-tumor effects and minimal accompanying side effects. Meanwhile, considering its excellent photothermal properties, photoacoustic imaging technology was utilized to provide comprehensive guidance for the precise localization of tumors in mice. The study shows that rational modification of traditional aza-DP-based synergistic phototherapy agents can yield unexpected enhancements in their therapeutic effects, providing new ideas for anti-tumor drug development.
研究领域:
药物化学
·
生物成像
·
光疗
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 52
·46159-46169
·
IF 3.289
Mingjia Chen,Chunmei Gao,Shaoyu Lü,Yuanmou Chen,Mingzhu Liu
An ideal tumor drug delivery platform should offer little release of the drug in a physiological environment and fast release of the drug once endocytosis into the tumor tissues occurs. Therefore, we have developed a new kind of core-crosslinked copolymers (mPEG-St-SeSex) based on mPEGylated starch and diselenide bonds for rapid drug release. The corresponding core-crosslinked analogs mPEG-St-SSx and mPEG-St-CCx copolymers using 3,3′-dithiodipropionic acid and octanedioic acid as crosslinkers, respectively, were synthesized and used as controls. The results displayed that all amphiphilic core-crosslinked copolymers could form micelles with spherical structures in aqueous solution, showing advanced stability compared to non-crosslinked micelles (mPEG-St) in physiologically related and ultra micelle destabilization conditions. The disassembly of micelles triggered by DTT, combined with in vitro drug release assay and intracellular drug release studies using confocal laser scanning microscopy (CLSM), indicated that the DOX-loaded mPEG-St-SeSex micelles showed higher activity and could be more quickly disrupted than the DOX-loaded mPEG-St-SSx and mPEG-St-CCx micelles in reducing environment and subsequently rapidly released drug. These results, in addition to cell cytotoxicity studies, demonstrated that the mPEG-St-SeSex micelles have the potential to develop controlled drug-delivery systems for cancer therapy.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2018
·
IF 6.014
Xichuan Tang,Liwei Tan,Kun Shi,Jinrong Peng,Yao Xiao,Wenting Li,Lijuan Chen,Qian Yang,Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) in vitro . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm 3 or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm 3 ) or normal saline as control (larger than 2000 nm 3 ). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Macromolecular Science Part A-Pure and Applied Chemistry
·
2014
·
IF 0.74
Yunyan Xue,Dandan Ma,Tianzhu Zhang,Siyan Lin,Shengnan Shao,Ning Gu
In this study, a series of comb-like methoxy polyethylene glycol (MPEG) functionalized polyurethanes (PUs) (PU–g–MPEG) were successfully prepared via ‘click’ chemistry and polyaddition reaction. The copper catalyzed Huisgen 1,3-dipolar cycloaddition was firstly carried out between 3,5-bis(hydroxymethyl)-1-propargyloxybenzene (PBM) and methoxy polyethylene glycol azide (MPEG–N3) to obtain MPEGylated diol PBM (MPEG–PBM). Then, the comb-like PUs having MPEG located on the backbones (PU–g–MPEG) were synthesized through the polyaddition of MPEGylated diol PBM and hexamethylene diisocyanate (HDI). Fourier transform infrared (FTIR), 1H NMR spectroscopy, size exclusion chromatography (SEC), and thermo gravimetric analyses (TGA) were used to characterize these synthesized MPEG-functionalized comb-like PUs (PU–g–MPEG). Compared with PU without MPEG grafts, PU–g–MPEG show a better wettability.
研究领域:
高分子化学
·
材料科学
·
有机合成
·
表面化学
✓ 已验证
DOI
高影响因子
DYES AND PIGMENTS
·
2024
·
IF 4.1
Zhijia Sheng,Chao Zhao,Xiaoyan Huang,Jing Wang,Yi Liu
Hypoxia is a common feature of solid tumors and is considered to be the fatal flaw of conventional photodynamic therapy (PDT), which severely reduces the overall therapeutic efficacy. Here, we developed a series of halogenated photosensitizers to address this issue. The results showed that the introduction of heavy atoms enhanced the spin-coupling effect of the photosensitizers and effectively improved the type I PDT (non-oxygen-dependent) efficiency. The preferred iodine-substituted photosensitizer NRh–I was used as the basic architecture, and further nitrosyl modification was performed to obtain the NO small-molecule prodrug, which was finally encapsulated with DSPE-mPEG 5k to obtain a biocompatible NO nanophotocontrolled prodrug. By using the enhanced permeability and retention effect (EPR), the prodrug system can precisely target the lesion site, release a high concentration of NO by photocontrol, kill the tumor cells, and at the same time, cascade with ROS released with the same “time-space” precision to generate higher cytotoxicity, ONOO − , which generates a stronger targeted synergistic therapeutic effect. This “butterfly effect” strategy maximizes the effect of PDT and broadens the idea of translational medicine.
研究领域:
癌症治疗
·
药学
·
生物医学工程
·
化疗
✓ 已验证
DOI
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 73
·45978-45986
·
IF 3.108
Na Wen,Chunmei Gao,Shaoyu Lü,Xiubin Xu,Xiao Bai,Can Wu,Piao Ning,Shaofei Zhang,Mingzhu Liu
The high pKa (8.26 to 8.6) of PBA has restricted its glucose-responsiveness in physiological conditions, and the high cytotoxicity of polymers is also a limiting problem in their potential application for insulin delivery. Novel amphiphilic glucose-sensitive dialdehyde starch polymers containing 3-aminophenylboronic acid (APBA) as a glucose-responsive group and mPEGylated dialdehyde starch (mPEG-DAS) with hydrophobic 7-hydroxycoumarin-4-acetic acid (Cou) were synthesized. This dialdehyde starch derivative can self-assemble into mPEG-DAS–APBA–Cou micelles with “shell–core” structures in phosphate-buffered saline solution (PBS). In addition, the drug-loaded micelles can release insulin rapidly in response to hyperglycemia in a physiological environment. The results demonstrated that the mPEG-DAS–APBA–Cou micelles showed notable glucose responsive behavior near the physiological range. The insulin release from the nanocarriers is sensitive to different concentrations of glucose, releasing insulin rapidly under the conditions of 3 mg mL−1 glucose while demonstrating comparatively inert release at 1 mg mL−1 glucose (pH 7.4). MTT assays and hemolysis studies both confirmed that the mPEG-DAS–APBA–Cou micelles have low cytotoxic activity to A549 cells and low blood toxicity. These results suggest that the glucose-sensitive dialdehyde starch micelles (mPEG-DAS–APBA–Cou) have potential applications as a glucose-responsive material for insulin delivery.
研究领域:
药学
·
纳米技术
·
生物材料
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2016
·
IF 4.342
Haijun Zhao,Qian Li,Zehui Hong
Although PEGylation allows a drug delivery vehicle to have prolonged blood circulation time, it faces the problem of reduced cellular uptake. Removal of the polyethylene glycol (PEG)-shell at the appropriate time through tumor-microenvironment triggers could be a feasible solution to this problem. Here, paclitaxel (PTX)-loaded mixed micelles (PTX-mM) self-assembled from stearate-modified hyaluronic acid (SHA), mPEG-b-poly(β-amino ester) (mPEG-b-PAE), and ethylene acetyl-b-poly(β-amino ester) (EA-b-PAE) were developed. In the preparation of PTX-mM, SHA micelles were coated with EA-b-PAE followed by coloading of PTX and mPEG-b-PAE. PTX-mM were capable of extracellular pH-triggered PEG-detachment and poly(β-amino ester) (PAE)-mediated endosomal escape. When the pH was changed from pH 7.4 to pH 6.8, the particle size of PTX-mM significantly decreased from 97.5 ± 4.4 to 71.5 ± 2.3 nm. It also resulted in rapid and complete release of mPEG-b-PAE from PTX-mM as monitored using quartz crystal microbalance (QCM) technology. PTX-mM capable of PEG detachment provided significant enhancement of PTX accumulation in SKOV-3 cells compared to PEG nondetachable PTX-mM. Interestingly, intracellular transport studies using confocal laser scanning microscopy (CLSM) showed that EA-b-PAE could promote the escape of micelles from endolysosomes. The half-maximal inhibitory concentration (IC50) of PTX-mM against SKOV-3 cells was 5.7 μg/mL, and PTX-mM containing 20 μg/mL of PTX induced apoptosis in 53.0% of the cell population. PTX-mM exhibited a highly prolonged elimination half-life (t1/2, 2.83 ± 0.37 h) and improved area under the curve (AUC, 7724.82 ± 1190.75 ng/mL/h) than the PTX-loaded SHA micelles (PTX-M). Furthermore, PTX-mM showed the highest tumor inhibition rate (64.9%) and the longest survival time (53 days) against the SKOV-3 ovarian cancer xenograft models among all formulations. Taken together, the results suggested that PTX-mM have potential as an efficient anticancer formulation in treatment of ovarian cancer.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Jinbiao Gao,Baiqing Yu,Chao Li,Wei Wang,Ming Xu,Zhong Cao,Xiaoyan Xie,Jie Liu
Gene therapy is one of the promising solutions in cancer therapeutics. Ultrasound-mediated gene delivery showed great potential as a noninvasive strategy for gene therapy. However, the efficiency of gene transfection and incorporation of multiple functions remain key challenges in the development of gene delivery systems. In this study, we developed perfluoropentane (PFP) and gold nanorods (AuNRs) loading nanodroplets for photothermal-enhanced ultrasound-mediated imaging and gene transfection. The nanodroplet theranostic system was formulated with fluorinated cationic poly(aspartamide) based polymer that encapsulated PFP, AuNRs, and plasmid DNA and was stabilized with a negatively charged poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) coating. The nanodroplets presented good stability, biocompatibility, and DNA binding stability. Upon treatment with both near-infrared and ultrasound energy, the photothermal and ultrasound-responsive system exerted a synergistic effect, in which strong adsorption of light induced hyperthermia that promoted the phase transition of PFP and the following ultrasound irradiation, generating strong acoustic cavitation and sonoporation, thus leading to enhanced ultrasound contrast imaging and gene transfection efficiency both in vitro and in vivo.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
分子生物学
·
医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Jian-Jiang Lu,Qi Shen,Xiao-Ying Li,Fei-Yun Sun,Jun-Bo Yi,Wen-Yi Dong,Wei-Jia Yan,Hong Du,Jia-Le Mu
Undesired long start-up time and unstable denitrification performance are major bottlenecks for engineering application of methane-based membrane biofilm reactors (MBfRs). In this study, two surface-manipulated membranes by respectively coating dopamine (DOPA) and grafting methoxy-poly(ethyleneglycol)-amine (mPEG-NH 2 ) onto the base polypropylene (PP) membrane were prepared, and for the first employed to aerobic methane oxidation coupled to denitrification (AME-D) process in MBfRs for quick biofilm formation and improving denitrification performance. The experiments demonstrated that the modified membranes, especially for PP/DOPA/mPEGNH 2 membrane, accelerated biofilm formation, and then shorten above 31% start-up time compared to the base PP membrane. Meanwhile, the biofilm detachment resistances also improved in the MBfRs employing the modified membrane. Extended Deraguin-Landau-Verwery-Oxerbeek (XDLVO) theory analysis indicated these benefits mainly attribute to enhanced interfacial interaction energy, which is significant to microbial initial attachment onto membrane surface. 16S rRNA gene analysis demonstrated the modified membrane also preferentially increased the abundances of key microorganisms at initial stage. These findings revealed the importance of quick biofilm formation and robust detachment resistance by involving surface-manipulated membranes onto maintaining MBfRs efficiency and stability.
研究领域:
环境工程
·
微生物学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Polymer Materials
·
2024
·
IF 4.4
Zhanhong Zheng,Dunsheng Liang,Henghui Deng,Jing Wang,Chaoqun Zhang
Developing plant oil-based waterborne polyurethane (WBPU) materials with both antibacterial and antifouling properties remains a great challenge. In this study, a range of amphiphilic soybean oil-based polyols were successfully synthesized by grafting poly(ethylene glycol) monomethyl ether (mPEG) onto the long fatty acid chains of epoxidized soybean oil (ESO) through a ring-opening reaction. Subsequently, the obtained polyols were utilized to prepare cationic WBPU dispersions. The results demonstrated that the biobased WBPU dispersions prepared from amphiphilic soybean oil-based polyols exhibited excellent stability compared to those prepared from traditional hydrophobic soybean oil-based polyols. In addition, the introduction of mPEG side chains enhanced the phase mixing of the soft segments in the WBPU network, resulting in a remarkable increase in the elongation at the break of the resulting WBPU films, which reached up to 745%. Furthermore, the soybean oil-based WBPU films containing mPEG side chains exhibited enhanced antibacterial and antifouling properties. Specifically, the amount of protein adhesion in the resulting WBPU films could be reduced by approximately 60%. The antibacterial rate against Staphylococcus aureus (S. aureus) was increased from 79.4% to 91.8%, while the rate against Escherichia coli (E. coli) increased from 78.2% to 92.3%. The resulting plant oil-based WBPU, with its excellent antibacterial and antifouling properties, holds promise for various medical and healthcare applications, including antibacterial wound dressings.
研究领域:
材料科学
·
聚合物化学
·
生物医学工程
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）