ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
研究领域:
药学
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癌症研究
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纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2018
·
IF 3.789
Baoping Lu,Xuna Yuan,Yuehong Ren,Qinghua Shi,Song Wang,Jinlong Dong,Ze-dong Nan
We describe a facile method to synthesize a new type of catalyst by electrodepositing Ag nanocrystals (AgNCs) on the different polymer dyes, Poly (methylene blue) (PMB) or Poly (4-(2-Pyridylazo)-Resorcinol) (PAR) modified graphene‑carbon spheres (GS) hybrids. The self-assembled GS take dual advantages of carbon spheres and graphene. Carbon spheres acts as nano-spacers prevent the aggregation of graphene and guarantee the fast electron transfer of GS. Secondly, polymerized dyes used here are beneficial for AgNCs growing as a linker. The effects of dyes on the growth habits, morphologies and catalytic properties for AgNCs were investigated. A novel electrochemical nonenzymatic sensor for hydrogen peroxide (H 2 O 2 ) detection is fabricated based on the Ag/Polymer dyes/GS ternary composites modified glass carbon electrode (GCE) for the first time. It was found that the proposed electrodes, especially for Ag/PMB/GS/GCE, displayed a peculiar electrocatalytic activity towards H 2 O 2 reduction synergistically as compared to Ag/PAR/GS/GCE or Ag/GS/GCE alone. Ag/PMB/GS/GCE showed a linear response over the H 2 O 2 concentration range of 0.5 to 1112 μM. The detection limit and sensitivity is 0.15 μM and 400 μA mM −1 cm −2 , respectively. These outstanding results enable the practical application of Ag/PMB/GS/GCE for the H 2 O 2 tracking released from MCF-7 (human breast cancer cells) with satisfactory results.
研究领域:
材料科学
·
纳米技术
·
分析化学
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生物传感器
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Caochuan Feng,Xiaoxiong Han,Lili Chi,Jing Sun,Feirong Gong,Yaling Shen
Combination therapy of two or more drugs has gradually become of outmost importance in cancer treatment. Cabazitaxel (CTX) is a taxoid drug and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of TNF superfamily. In this study, we prepared TRAIL-modified and CTX-loaded polymer micelle (TRAIL-M-CTX). This nanoparticle was self-assembled from biodegradable amphiphilic copolymers, monomethoxyl poly(ethylene glycol)–b-poly(DL-lactide) (mPEG-PLA) and COOH-PEG-PLA, via a nanoprecipitation method and were modified with the TRAIL protein, resulting in a particle size of 39.75 ± 0.17 nm in diameter and a drug encapsulation efficiency of 95.52 ± 1.69%. The successful coupling was confirmed by 1H NMR, FTIR spectroscopy, and DLS article size measurement. Pharmacodynamic analysis in two human cancer cell lines with different TRAIL sensitivities showed that TRAIL-M-CTX has a significantly better anticancer efficacy than the individual CTX and TRAIL protein. Importantly, TRAIL-M-CTX showed synergistic effects against TRAIL-insensitive cells (MCF-7). A study of cellular uptake implied that the modified micelles were internalized into MCF-7 cells more effectively than unmodified micelles, owing to the coupled TRAIL protein. A cell cycle assay of MCF-7 cells revealed that TRAIL-M-CTX significantly increased the sub-G1 population compared with CTX or TRIAL, thus, facilitating cancer cell apoptosis. These results suggest that TRAIL-M-CTX micelles have potential as a cancer chemotherapy formulation.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 30
·5011-5020
·
IF 4.776
Jinyu Li,Yue Yang,Yibin Yu,Qi Li,Guoxin Tan,Yuanyuan Wang,Wei Liu,Weisan Pan
The synthetic clay material, LAPONITE® (LAP), having a nanodisk structure together with a negatively charged surface, has been used for effective drug encapsulation by virtue of its interlayer space. In this research effort, the LAP nanodisk was used for the first time to encapsulate the antifolic methotrexate (MTX); the MTX-loaded LAP nanodisks (LAP/MTX) demonstrated a high drug loading efficiency of 80.39%. An efficient and reliable tumor-targeting device that rests on the synthesized oligomeric hyaluronic acid-L-histidine (oHA–His) was then encapsulated in the MTX-loaded LAP disks (forming LAP/MTX/oHA–His nanohybrids). The drug released from the LAP/MTX/oHA–His nanohybrids was pH-dependent and matched the first-order kinetics that describes the diffusion mechanism. In vitro biological evaluation manifested that the MTX-loaded LAP nanocarriers, particularly the LAP/MTX/oHA–His nanohybrids that have targetability and lysosomal antineoplastic activity, can be effectively internalized by the MCF-7 cell line, and can exhibit a more prominent anticancer cytotoxicity than free MTX. In vivo studies with mice indicated that the LAP/MTX/oHA–His nanohybrids demonstrated much higher antitumor efficiency compared to the LAP/MTX nanohybrids and pure MTX. Taken together, the LAP/oHA–His, CD44 receptor targeting and pH-sensitive multifunctional nanohybrids conferred the MTX with excellent cytocompatibility, dispersion stability, sustained pH-responsive release properties, and improved anticancer activity, and may be further developed as a potential active nanoplatform for various anticancer drugs.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Lijun Hu,Min Li,Zhipeng Zhang,Yuanyuan Shen,Shengrong Guo
Paclitaxel (PTX), one of the most potent anticancer agents , has showed a remarkable activity against varieties of tumors. However, the bioavailability of PTX is quite low due to its poor aqueous solubility. Moreover, the emerging multidrug resistance (MDR) in cancer to PTX remains a major obstacle for successful chemotherapy. In order to address these problems, we developed self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) (Biotin-PEG-PCDA) for PTX delivery (termed as PTX-BPC NPs) with the application of mPEG 2K -P(CL-co-LLA) as an emulsifier . The loading content and encapsulation efficiency of PTX were 13.2% and 92.0%, respectively. In vitro drug release study showed that PTX-BPC NPs could degrade rapidly and then release the PTX payload in a 10 mM glutathione (GSH) environment. Compared with free PTX, PTX-BPC NPs exhibited enhanced anticancer efficacy (IC 50(MCF-7/ADR cells) , 17.28 µg/mL vs. 1.15 µg/mL). In addition, these biotin-modified nanoparticles could also significantly reverse PTX resistance by suppressing the over-expression of P-gp, thus resulting in increased intracellular drug accumulation and reduced drug efflux in MCF-7/ADR cells, which showed a great anticancer effect.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 110
·90386-90395
·
IF 3.84
Weihua Jiang,Ju Wang,Lei Yang,Xuewei Jiang,Zhaoshi Bai,Zheran Wang,Yunpeng He,Dongkai Wang
An amphiphilic carboxymethylcellulose-graft-histidine/methoxypolyethylene glycol (CMP) copolymer was firstly synthesized to modify nanostructured lipid carriers (NLCs), and the impact of this CMP modification on in vitro and in vivo behaviors of NLCs was investigated in detail. An obvious core–shell structure of CMP-coated nanostructured lipid carriers (CNLCs) was observed by a transmission electron microscope (TEM). Docetaxel (DTX) efficiently encapsulated in CNLCs formed 88.7 ± 1.11 nm particles with a negative zeta potential of −20.9 ± 1.11 mV. In vitro release studies indicated that the CMP coating significantly reduced the burst drug release at pH 7.4, whereas DTX-loaded CNLCs (DTX-CNLCs) could release the drug as quickly as DTX-loaded NLCs (DTX-NLCs) at pH 5.0. The pharmacokinetic performances proved that DTX-CNLCs had longer retention times in blood and higher area under the concentration–time curve (AUC) in rats than DTX-NLCs (p < 0.05). Furthermore, cell uptake, cytotoxicity, and cell apoptosis assays in MCF-7 cells consistently demonstrated that no obvious difference was found between DTX-CNLCs and DTX-NLCs (p > 0.05), indicating that this modification did not disturb effective killing of the cancer cells. As expected, DTX-CNLCs exhibited better antitumor effects than DTX-NLCs in the tumor-bearing nude mice (p < 0.05), due to their long circulation effect. Consequently, CNLCs hold great potential for effective delivery of anticancer drugs.
研究领域:
药学
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生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 9
·1712-1723
·
IF 4.543
Rui He,Mingxian Liu,Yan Shen,Zheru Long,Changren Zhou
Here, polystyrene sulfonate sodium (PSS) modified Halloysite nanotubes (HNTs) were self-assembled into a patterned coating on a glass substrate with ordered nanotube arrays in a slit-like confined space. The microstructure of the formed patterned HNTs coating was investigated. The formed strips are more regular and almost parallel to each other with an increase in HNTs concentration. The HNTs coating formed from the 2% PSS-HNTs dispersion has the maximum nanotube alignment degree. The patterned HNTs coating was employed to capture tumor cells. The tumor cells can be captured by the HNTs coating effectively compared with a smooth glass surface due to the enhanced topographic interactions between the HNTs coating and cancer cells. The HNTs coating prepared from the 2% PSS-HNTs dispersion has the highest capture yield which is due to the ordered nanotube arrangement and the appropriate surface roughness. The HNTs coating was further conjugated with anti-EpCAM, which leads to the capture yield of MCF-7 cells reaching 92% within 3 h. The HNTs coating can capture 8 MCF-7 cells from 1 mL artificial blood samples spiked with 10 MCF-7 cells, showing the promising applications of HNTs in clinical circulating tumor cell capture for early diagnosis and monitoring of cancer patients.
研究领域:
纳米技术
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生物材料
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemNanoMat
·
2021
·Vol. 7
·期 12
·1361-1368
·
IF 3.154
Zhaoyu Han,Yue Qian,Yiyang Wu,Yanfei Cai,Jian Jin,Zhaoqi Yang
Graphical A hybrid drug delivery system based on ZIF-90 encapsulated with Doxorubicin and Ce6-G3139 has been established to induce apoptosis for enhanced chemotherapy. Metal-organic frameworks are highly porous and biodegradable and have found numerous applications in biomedicine. However, the traditional chemotherapy of MOF-drug delivery system remains a great challenge because of adverse side effects and cell tolerance. In this work, we have fabricated a hybrid drug delivery system based on ZIF-90 encapsulated with Doxorubicin (DOX) and Ce6-G3139 for enhanced chemotherapy. The released DOX can enter cell nucleus and trigger cell death. In addition, the G3139 binds to the anti-apoptotic gene Bcl-2 in tumor cells and related proteins are downregulated to inhibit cell proliferation. Meanwhile, the photosensitizer Ce6 carried by the nucleic acid will generate abundant reactive oxygen species under a near-infrared (NIR) laser irradiation thus induces more cell apoptosis. It was worth mentioning that in vitro MTT test in the MCF-7 cells assays revealed that DOX@ ZIF-90/Ce6-G3139 nanoparticles possessed stronger anticancer capability than free DOX or DOX@ ZIF-90 nanoparticles indicating that the investigation offers an exciting new therapeutic strategy for the treatment of chemotherapy.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
·
药学
✓ 已验证
产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Bo Zhang,Xiu-Ting Hu,Kang-Min Zhou,Yu-Shun Yang,Hai-Liang Zhu
Cyclooxygenase is critical for maintaining physiological functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that Z21 displayed excellent COX-2 inhibitory activity against COX-2 (IC 50 = 0.22 ± 0.04 µM) and anti-proliferative activity against MCF-7 cell (IC 50 = 4.37 ± 0.49 µM). The apoptosis induction of compound Z21 was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound Z21 induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Yang Yu,Lixin Fan,Chunling Gao,Yang Ping,Liting Mu,Weitong Sun
Despite the advances made in cancer treatment, malignant tumors remain a significant threat to human health. Tumor multidrug resistance (MDR) constitutes a significant impediment to the effectiveness of chemotherapy. Thus, the reversal of MDR has become a critical research domain for medical professionals. Now, paclitaxel (PTX) is encapsulated in a reduction-sensitive polymer pre-drug micelle called mPEG-SS-IND(PSI), which reduces the MDR of PTX and enhances its anti-tumor efficacy. The PSI/PTX micelles show excellent reduction sensitivity and stability. In vitro , the harmful effect of PTX on MCF-7/PTX cells is enhanced by the PSI/PTX micelles, while its damaging effect on normal cells is decreased. Furthermore, compared to PTX solution, PTX encapsulated in PSI/PTX micelles exhibits reduced volume distribution and clearance, longer blood circulation time, and greater drug concentration area under the curve. Furthermore, in vivo studies using BALB/c subcutaneous tumor-bearing mice demonstrate decreased systemic toxicity and enhanced therapeutic effectiveness of PTX. This study proves that the potential utility of reduction-sensitive polymer pre-drug micelles as a delivery method for overcoming MDR for PTX and targeting tumors.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yanan Kang,Lu Lu,Jinshuai Lan,Yue Ding,Jing Yang,Yong Zhang,Yuan Zhao,Tong Zhang,Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers , which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy , flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer. Statement of Significance The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin , methotrexate and other drugs with carboxy groups in their structure.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2018
·Vol. 34
·期 2
·229-234
·
IF 1.248
Yu Yang,Ma Wei,Yu Lina,Zhou Shuyuan,Zhu Guangshan,Shi Wei
In this paper, antibody-modified silica nanoparticles were successfully synthesized, and their average di-ameter was (109±9) nm. These particles were mixed with cell extracts to target a protein, then, an antibody labeled with fluorescein isothiocyanate(FITC) was added to form FITC-labeled nanoparticle complexes and the product was analyzed using flow cytometry. The results confirm that the intracellular proteins and biomarkers were precisely and sensitivity detected by the novel method in vitro . The FITC intensity of Akt antibody-conjugated particles was in-creased ≥10-fold compared with that of control samples in MCF-7 cells. Furthermore, it can also simultaneously measure several proteins when modified with different antibodies.
研究领域:
纳米技术
·
生物化学
·
细胞计量学
·
蛋白质组学
·
癌症研究
✓ 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）