Polymers
·
2019
·Vol. 11
·期 2
·262
·
IF 3.164
Peng Zhang,Jiaying Hu,Leran Bu,Hena Zhang,Baixiang Du,Caihong Zhu,Yuling Li
In this paper, we synthesized a biodegradable amphiphilic polymer of polyurethane-polyethylene glycol with disulfide bonds in the main chain (PEG-PU(SS)-PEG). DLS and SEM showed that the polymer could self-assemble into micelles in aqueous solution and could be used to load the hydrophobic anticancer drug DOX. Intriguingly, drug release in vitro indicated that DOX-loaded PEG-PU(SS)-PEG micelles had good stability under the extracellular physiological environment, but the disulfide bonds broke rapidly and DOX was released quickly under the intracellular reducing conditions. CCK-8 assays showed that DOX-loaded PEG-PU(SS)-PEG micelles had a high in vitro antitumor activity in C6 cells, whereas blank PEG-PU(SS)-PEG micelles were nontoxic to C6 cells. It was also found that there was strong and persistent accumulation of DOX-loaded PEG-PU(SS)-PEG as compared with PEG-PU-PEG both by the cell internalization tests and the flow cytometry measurements. Hence, PEG-PU(SS)-PEG micelles will have a potential use for clinical treatment of cancer in the future.Keywords:reduction-responsive;micelles;polyurethane;triggered release
研究领域:
生物材料
·
肿瘤学
·
药物递送
✓ 已验证
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2020
·Vol. 298
·期 8
·1119-1128
·
IF 1.536
Wang Qiang,Gao Feng,Zhou Xianyong
Compared with conventional drug nanocarriers, multifunctional drug delivery systems exhibited characteristic advantages. In this study, we developed a multifunctional drug delivery system possessing stimuli-responsive drug release and cellular imaging. Amphiphilic polymers, methoxypolyethylene glycol-cystamine-tetraphenylethene (mPEG 1k -SS-TPE), were synthesized by combining methoxypolyethylene glycol (mPEG 1k ) and tetraphenylethene (TPE) using reduction-sensitive disulfide bonds that can be disconnected by high level of inherent glutathione (GSH). Size distribution and morphology of mPEG 1k -SS-TPE micelles were evaluated. Meanwhile, the reduction-sensitivity of mPEG 1k -SS-TPE micelles was surveyed compared with that of mPEG 1k -TPE micelles. Nile Red was encapsulated into mPEG 1k -SS-TPE micelles to visually observe intracellular drug delivery against SW480 cells. Paclitaxel (PTX) was chosen to be loaded into micelles to evaluate the cytotoxicity against HCT116, HT-29, and SW480.
Graphical Abstract
研究领域:
生物材料
·
药物化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Current Drug Delivery
·
2024
·Vol. 21
·期 2
·295-307
·
IF 2.8
Yang Yaxin,Shi Wei,Zhang Ziyi,Gong Fawu,Feng Xuman,Guo Chenxi,Qi Yajuan,Liu Zhanjun
Introduction: Anti-inflammatory medications, in particular aspirin, have chemopreventive and anticancer adjuvant effects on specific types of cancers, according to ongoing anti-tumor research. Additionally, efforts have been made to transform Poly(salicylic acid) (PSA) into delivery-related
nanocarriers. to transport anticancer medications into nanocarriers. However, tumor cell targeting and tumor selectivity were lacking in the salicylic acid polymer-based nanocarriers, preventing them from performing to their full potential. Objective: The objective of this study is to
prepare targeting and reduction-responsive poly pre-drug nanocarriers (HA-ss-PSA NPs) and to investigate the feasibility of delivering adriamycin (DOX) as nanocarriers. Methods: The structures of the polymers were confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR)
and infrared spectroscopy (IR); the encapsulation rate and drug loading of DOX-loaded nanoparticles were determined by HPLC; and the anti-tumor effects of the carriers were evaluated by MTT experiments and in vivoexperiments. Results: The prepared nanocarriers had uniform particle
size distribution. The drug release rate was up to 80% within 48 h in the tumor environment. DOX/HA-ss-PSA NPs showed significant cytostatic effects. In addition, HA-ss-PSA NPs showed significant targeting and inhibition of cell migration in cell uptake and scratch assays. In vivoexperiments
showed that the prepared carriers had high tumor inhibition rates, good targeting effects on the liver and tumor, and significantly reduced toxicity to other tissues. Conclusion: The prepared HA-ss-PSA NPs could effectively inhibit the growth of HepG2 cells and tumors in vivo,
indicating that PSA could be used as a backbone component of a safe and reliable drug delivery system, providing a new strategy for the treatment of liver cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 22
·10514-10527
·
IF 7.233
Hang Hu,Jiangling Wan,Xuetao Huang,Yuxiang Tang,Chen Xiao,Huibi Xu,Xiangliang Yang,Zifu Li
Herein, reduction-responsive disintegratable nanoclusters (NCs) were prepared as a novel nanovehicle for targeted drug delivery. The NCs, with a diameter of ∼170 nm, were self-assembled from hydrophobically modified and iRGD decorated hydroxyethyl starch (iRGD-HES-SS-C18). DOX was loaded into the NCs as a model drug. DOX@iRGD-HES-SS-C18 NCs can disintegrate into smaller ones and release DOX under reduction stimuli. Due to the ligand–receptor binding interactions between iRGD and integrin αV, DOX@iRGD-HES-SS-C18 NCs can specifically bind to the cell membranes of HepG-2 and 4T1 cells (integrin αV positive), resulting in enhanced cellular uptake as compared to DOX@HES-SS-C18 NCs. After cellular internalization, the NCs were transported to endosomes/lysosomes in which the reductive environment triggered the disintegration and DOX release. As a consequence, DOX@iRGD-HES-SS-C18 NCs exhibited an enhanced antitumor effect as compared to DOX@HES-SS-C18 NCs and free DOX, in an in vitro antitumor activity study. The reduction-responsive disintegratable NCs reported here were proved to be a safe and efficient nanoplatform, holding significant translation potential for tumor-targeted drug delivery.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Yayuan Guan,Yuling Su,Lili Zhao,Fancui Meng,Quanxin Wang,Yongchao Yao,Jianbin Luo
Polyurethane micelles with disulfide linkage located at the interface of hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug release profiles. However, the payloads could not be released completely. The occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG coronas was considered as the reason for the incomplete release. To verify the above hypothesis and to develop a new polyurethane based micelles with dual stimuli respond properties and controllable location of pH and reduction responsive groups in the PU main chains, a tertiary amine was incorporated into the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide linkages located between the hydrophilic PEG segment and the hydrophobic PCL segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen as mode hydrophobic drug to evaluate the loading and redox triggered release profiles of the PU micelles. It was demonstrated that PU-SS-N micelles disassembled instantly at the presence of 10 mM GSH and at an acidic environment (pH = 5.5), which resulted the nearly complete release (~ 90%) of the payloads within 48 h, while about ~ 70% PTX was released from PU-SS-I and PU-SS-N micelles at neutral environment (pH = 7.4) with the presence of 10 mM GSH. The rapid and complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will be a promising anticancer drug delivery system to ensure sufficient drug concentration to kill the cancer cells and to prevent the emergency of MDR. The in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also assessed in H460 and HepG2 cells.
研究领域:
材料科学
·
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Dong Wan,Chao Li,Jie Pan
In order to overcome the deficiencies of conventional nanotechnology-based drug delivery systems such as a short circulation time in blood, lack of tumor targeting, slow drug release in the interior of cancer cells, and so on, reduction-responsive polymeric micelles developed in this study with copolymers of TPGS3350-SS-DTX and TPGS3350-folate were triggered for cancer-targeted drug delivery. The layer of TPGS3350 in micelles was used to stabilize micelles and enhance the circulation period of micelles in blood. Once the micelles accumulated at the tumor region by EPR effect, tumor cells could ingest these micelles by the pathway of folate-receptor-mediated endocytosis. Next, fast drug release in cancer cells was achieved under the effect of high level of glutathione (GSH) inside cancer cells. The micelles invented in this study demonstrated various functions comprising active targeting, extended circulating life in blood, fast intracellular drug release, and so on. It can be noticed from findings in this research that these cooperative functions in micelles could significantly promote chemotherapeutic effectiveness and reduce their toxic side effects. Moreover, this work provides a drug delivery strategy to explore the feasibility of application reduction-responsive micelles for chemotherapy in clinic.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
Therapeutic Delivery
·
2025
·
IF 2.2
Lixin Fan,Yang Yu,Kunpeng Shi,Yanqiu Hu,Xingyu Hou,Weitong Sun
Objective The presence of overexpressed folate-receptor and high concentration of glutathione (GSH) in liver cancer cells has been exploited and we have synthesized Folic acid-Dextran-Cystamine-Stearic acid (FDCS) for efficient and multifunctional delivery of the drug sorafenib (SAF) to enhance the anticancer effects.Methods The characteristics of micelles such as physicochemical properties and in vitro release were investigated. The pharmacokinetic characteristics of the micelle and SAF groups in rats were investigated. In vitro and in vivo anti-tumor experiments were performed with HepG2 cells.Results SAF-FDCS was successfully prepared and characterized. The cellular experiments showed that SAF-FDCS significantly enhanced the toxicity and inhibitory effects on HepG2 cells compared with free drug and the other micelles without smart response, and the uptake capacity of cellular HepG2 for SAF-FDCS was significantly higher than the groups without folic acid. Pharmacokinetic results showed that SAF-FDCS revealed a longer circulation time than free SAF. In addition, the tumor inhibition rate of SAF-FDCS in the subcutaneous graft tumor model of HepG2 cells was 84.6%, significantly higher than in other groups.Conclusions These results demonstrated the feasibility of SAF-FDCS micelles in inhibiting tumor growth and their superiority in anti-cancer effects compared to free drugs and normal micelles.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Qiuya Lei,Runhao Guo,Xianglong Wu,Yanni Zhang,Ning Cui,Jian-Yu Shi,Tingli Lu
Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly (N-isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, PssNCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells.Methods: The PssNCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells.Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels.Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.
研究领域:
肿瘤学
·
药剂学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Biotechnology Journal
·
2025
·Vol. 20
·期 3
·e70006
·
IF 3.1
Jingyi Xiao,Zan Ge,Xiaowei Tan,Ziyi Liu,Yafang Zhang,Shufen Xiao,Rongyuan Yi,Ye Hu,Wenyan Hu,Hui Chu,Jian Chen
Traditional beta-cyclodextrin (beta-CD) in biomedical applications faces challenges due to its inherent physical and biochemical limitations. One of the most effective strategies to enhance the properties of beta-CD for drug delivery is the synthesis of supramolecular polycyclodextrins. In this study, we designed a novel beta-CD nanocage-like structure for drug delivery, incorporating imine and disulfide bonds through Schiff base reactions. Aldehyde group-functionalized beta-CD units were used to construct the main backbone of the nanocage, forming dual-dynamic covalent bonds. The chemical structure of the beta-CD nanocage was confirmed using ¹H nuclear magnetic resonance (¹H NMR) and Fourier transform infrared spectroscopy (FTIR). Additionally, atomic force microscopy (AFM) and dynamic light scattering (DLS) revealed that varying amounts of beta-CD crosslinked with cystamine resulted in nanocages approximately 200 nm in size. In vitro drug release experiments demonstrated that doxorubicin (DOX)-loaded beta-CD nanocages exhibited accelerated DOX release in acidic and reductive environments compared to normal physiological conditions, owing to the pH-sensitive imine bond and the glutathione (GSH)-cleavable disulfide bond. The DOX-loaded beta-CD nanocages showed exceptional tumor-killing effects, particularly in acid/reduction-enhanced tumor cells. Both cellular fluorescence imaging and flow cytometry confirmed the potential of the beta-CD nanocages for acid/reduction-specific drug release. Consequently, this precision medicine model using imine/disulfide-linked beta-CD nanocage structures as acidity/reduction-sensitive drug carriers promises to improve oncotherapy through more targeted drug delivery and release, supporting individualized treatment approaches.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2012
·Vol. 4
·期 4
·1199-1207
·
IF 5.321
Mingqiang Li,Zhaohui Tang,Hai Sun,Jianxun Ding,Wantong Song,Xuesi Chen
A novel pH and reduction dual-responsive nanogel with improved cellular internalization was prepared through atom transfer radical polymerization and subsequent quaternization reaction. Doxorubicin (DOX), a model anticancer drug, was loaded into the nanogel via dispersion. The DOX-loaded nanogel presented a stable core-cross-linked structure under physiological conditions, but quickly released its payload in an acidic (pH 6.8) and reductive (10.0 mM glutathione) environment. Confocal fluorescence microscopy and fluorescence flow cytometry revealed that the DOX-loaded nanogel could deliver DOX into the cytoplasm and nucleus of cells, more efficiently than that of free DOX. The improved cellular internalization was more significant under acidic and reductive conditions, which was analogous to the pH and reductive conditions in endosomes and cytoplasm. In vitro cytotoxicity studies demonstrated that the pH and reduction responsive DOX-loaded nanogel could inhibit cellular proliferation more efficiently than free DOX. This dual-bioresponsive nanogel with quaternary ammonium salt group has appeared to be highly promising in the further development of intracellular drug transporters.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Water Process Engineering
·
2021
·
IF 5.485
Longfeng Sun,Kai Xu,Xuefeng Gui,Lingli Liu,Qiong Lin,Xuan Song,Zhongxin Wang
Sulfur-containing polymers such as those with polysulfide linkages in their backbone have attracted strong interest due to the ease of modifying the structure and properties of these materials. Electrospun fiber membranes have large specific surface areas, adjustable microstructures and chemical properties, and recovery. Consequently, these materials are promising candidates for applications as sorbents for heavy metal enrichment and water remediation . Herein, polymeric sulfur–monoterpene (PST) was loaded into a polyvinylidene/poly(methyl methacrylate) (PVDF/PMMA) polymer matrix by electrospinning technology to obtain a uniform and continuous fiber-based membrane. It was found that treatment with a reducing agent increased the thiol group content in PST. Then, by using the coordination and binding effect between sulfhydryl groups and metal ions , it was found that the adsorption of Cd(II), Cr(III), Ni(II) and Hg(II) ions onto the membrane was enhanced under the stimulation of reduction. The results indicated that the reduction-responsive adsorption of Hg(II) and Cd(II) was the best, with maximum adsorption values of 58 and 34 mg g −1 for each of these respective ions. In addition, the presence of sodium ions did not interfere with the adsorption of Hg(II) or Cd(II) ions. The adsorption kinetics of Hg(II) and Cd(II) ions on the reduced membrane at different times were also studied. The results revealed that the adsorption of Hg(II) and Cd(II) ions onto the reduced membrane conforms to the pseudo-second-order kinetic model. These results indicated that PST can removal of heavy metal ions from wastewater via a convenient and reusable adsorption process .
研究领域:
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMACROMOLECULES
·
2017
·
IF 5.246
Feiran Zhang,Siman Gong,Jun Wu,Huipeng Li,David Oupicky,Minjie Sun
The unsatisfied results of cancer therapy are caused by many issues and metastasis of cancer cells is one of the major challenge. It has been reported that inhibiting the SDF1/CXCR4 interaction can significantly reduce the metastasis of breast cancer cells to regional lymph nodes and lung. Herein, a nanogel system equipped with the FDA-approved CXCR4 antagonist AMD3100 was developed and evaluated for its combined antimetastatic and tumor targeting effects. Briefly, a bioreducible cross-linked dextrin nanogel (DNG) coated with AMD3100 was designed to possess multiple functions, including CXCR4 chemokine targeting, inhibition of tumor metastasis, and reduction-responsive intracellular release of doxorubicin (DOX) to reduce the cells proliferation. The in vitro results confirmed that the DOX-loaded AMD3100-coated dextrin nanogel (DOX-AMD-DNG) was more effectively taken up by 4T1 breast cancer cells than DOX-DNG and was significantly more cytotoxic to 4T1 cells than DOX-DNG. In biodistribution studies, the stronger fluorescence intensity of Cy7-AMD-DNG than Cy7-DNG further confirmed that AMD3100 mediated tumor targeting in vivo. AMD3100-coated DOX-DNG also exhibited a distinct antimetastatic effect and CXCR4 antagonistic activity by inhibiting CXCR4-mediated cell invasion in 4T1 and U2OS cells. Moreover, DOX-AMD-DNG displayed superior anticancer activity and antimetastatic effects in orthotopic breast cancer-bearing Balb/C mice. In summary, the multifunctional DOX-AMD-DNG can effectively target the tumor site and dually impede cancer progression and metastasis.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）