EUROPEAN POLYMER JOURNAL
·
2016
·
IF 3.485
Changyu He,Qinglai Yang,Lianjiang Tan,Bingya Liu,Zhenggang Zhu,Bing Gong,Yu-Mei Shen,Zhifeng Shao
The need for smart materials in the area of biotechnology has accelerated the development of stimuli-responsive copolymer micelles. Here, we reported a novel dual-stimuli-responsive block copolymer PEG-DMTK-SS-PLA with both dimethyl thioketal (DMTK) and disulfide linkage incorporated into the backbone, capable of triggering fast drug release properties upon both oxidative (H 2 O 2 ) and reductive (GSH) environment. The CMC values of these copolymer micelles ranging from 0.051 to 0.087 mg mL −1 , the average diameters are from 34 nm to 55 nm and 65 nm to 198 nm for blank and DOX-loaded micelles respectively. MTT assay conducted in NIH 3T3 cells showed the low cytotoxicity of these micelles even when the concentration reached up to 500 μg/mL. Considering tumor microenvironment’s diverse in kinds of tumor cells, fluorescence microscopy, flow cytometry and MTT activity analysis were conducted in several cancer cells (e.g., cervix, lung, gastric, and colon cancer cells), and further confirmed that the dual responsive PEG-DMTK-SS-PLA micelles were degraded much faster than that of non-responsive PEG-PLA and single responsive PEG-SS-PLA and PEG-DMTK-PLA micelles. These results indicate that the dual-responsive micelles are promising for efficient anticancer drug delivery.
研究领域:
生物技术
·
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2012
·
IF 3.456
Qian Guo,Ping Luo,Yu Luo,Fang Du,Wei Lu,Shiyuan Liu,Jin Huang,Jiahui Yu
Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)- block -poly(γ-benzyl l -glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24 h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2015
·Vol. 293
·期 8
·2291-2300
·
IF 1.865
Zhou Qing-Han,Lin Juan,Li Li-Dong,Shang Le
Biodegradable micelles based on disulfide-linked monomethoxy poly(ethylene glycol)- b -poly(methyl methacrylate) 2 (mPEG-SS-PMMA 2 ) miktoarm star block copolymers were synthesized through atom transfer radical polymerization procedure and applied to solubilization and delivery of methotrexate (MTX). The synthesized miktoarm star block copolymers were characterized by 1 H nuclear magnetic resonance, Fourier transform infrared spectra, and gel permeation chromatography. The block copolymers were able to self-assemble into spherical micelles in water with an average diameter up to 130 nm by transmission electron microscopy observation and dynamic light scattering measurements and have a critical micelle concentration of 0.91 mg/L. When MTX was incorporated into obtained micelles, high drug loading capacity was found attributed to the designed miktoarm star-shaped nanostructure. Interestingly, in presence of dithiothreitol, the micelles could be degraded into polymer chains by cleavage of the disulfide linkages. The in vitro release studies revealed that these micelles released over 95 % of MTX within 48 h under a reductive environment analogous to that of the cell comparing to minimal drug release (<22 %) under nonreductive conditions. Cell cytoxicity experiments showed that the obtained micelles exhibited nontoxic, and the drug-loaded micelles exhibited high anticancer efficacy and better biocompatibility as compared to free MTX. All of these results showed that mPEG-SS-PMMA 2 micelles are promising carriers for delivery of hydrophobic antitumor drugs.
研究领域:
药学
·
高分子科学
·
纳米技术
·
药物传递
·
生物化学
·
材料科学
✓ 已验证
DOI
高影响因子
SHOCK
·
2024
·
IF 2.7
Liu Lijuan,Wang Ruoyu,Pu Xuexue,Zha Yutao,Yang Xiao,Fang Xiao,Liu Yong,Shao Min,Zhu Ling,Ren Xiaoou,Deng Guoqing,Yang Ke
Background Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. Methods We developed a novel method using the D 4 -Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug. Results Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells. Conclusions Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.
研究领域:
免疫学
·
传染病学
·
药理学
·
细胞生物学
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2013
·
IF 5.695
Shenfei Zong,Zhuyuan Wang,Hui Chen,Jing Yang,Yiping Cui
A surface enhanced Raman scattering (SERS) traceable nanocarrier is presented through a simple strategy for the intracellular redox environment triggered drug delivery. Basically, the nanocarrier has a core–shell structure, with the Raman molecule tagged Au@Ag nanorods as the SERS active core and mesoporous silica (MS) as the drug containing shell. In the presented system, the locations of nanocarriers can be tracked by SERS signals while those of drugs can be monitored through their fluorescence, allowing the simultaneous investigation of the intracellular distribution of both the nanocarriers and the drugs. To endow the nanocarrier with the glutathione (GSH) responsive behavior, disulfide, which can be cleaved by GSH, is used to directly attach drug molecules to the MS. Compared with other disulfide based drug delivery strategies, this is a quite simple and efficient method. The experimental results confirmed that the drug release can be triggered by the stimuli. Moreover, after the cellular uptake of the nanocarriers, a gradual drug release from the nanocarriers was observed by monitoring both the fluorescence of the drug molecules and the SERS signals of the nanocarriers. Considering its stimuli-responsive properties, this kind of nanocarrier would have great potential in improving the efficacy of cancer chemotherapy by avoiding premature drug leakage. More importantly, this SERS based tracking method of the nanocarrier would be more powerful than that based only on the fluorescence of the drug in the studies of drug release dynamic processes.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2018
·Vol. 18
·期 7
·1800022
·
IF 3.392
Xiao-Yan Tu,Chao Meng,Xiao-Long Zhang,Miao-Ge Jin,Xian-Shuo Zhang,Xue-Zhi Zhao,Yun-Fei Wang,Li-Wei Ma,Bao-Yan Wang,Ming-Zhu Liu,Hua Wei
The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA- g -PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a “grafting from” approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core–shell–corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.
研究领域:
高分子化学
·
药学
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）