CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Dan Gao,Sajid Asghar,Junxiu Ye,Mei Zhang,Rongfeng Hu,Yadong Wang,Lin Huang,Chengjun Yuan,Zhipeng Chen,Yanyu Xiao
In this study, a CD44 and biotin receptors dual-targeted enzyme-sensitive hyaluronic acid nanogel loading paclitaxel (PTX/Bio-NG) for targeting breast cancer was constructed. Spherical nanogels with a mean particle size of 149.1 ± 1.6 nm, higher entrapment efficiency (90.17 ± 0.52 %) and drug loading (15.28 ± 0.10 %) were obtained. PTX/Bio-NG quickly released drugs under the catalysis of hyaluronidase and/or lipase . Cell studies revealed that the uptake of Bio-NG by 4T1 cells was mediated by CD44 receptor and Bio-specific receptor. Compared with PTX-loaded biotin-free NG (PTX/NG), PTX/Bio-NG had higher cytotoxicity against breast cancer cells (4T1 cells). The rats pharmacokinetic profile indicated higher AUC 0-t but lower clearance rates of PTX/NG (6.24 times and 15.96 %, respectively) and PTX/Bio-NG (6.66 times and 14.89 %, respectively) than control group (Taxol). In vivo studies showed that PTX/Bio-NG possessed excellent therapeutic efficacy in 4T1 tumor-bearing Balb/c mice, which suggest that PTX/Bio-NG could be an excellent candidate for the treatment of breast cancer.
研究领域:
药学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 17
·3801-3813
·
IF 5.344
Dong Zhou,Sainan Liu,Yongjun Hu,Shiwei Yang,Bing Zhao,Kaikai Zheng,Yuhong Zhang,Peixin He,Guoyan Mo,Yulin Li
Lack of sufficient tumor penetration of the current nanomedicines is a major reason limiting their clinical success in cancer therapy. In this work, we aimed at the development of a novel biodegradable nanoplatform for the selective and controlled delivery of anticancer agents, with improved tumor permeability and the ability to release ultrasmall nanovesicles in the tumor microenvironment. To this end, positively charged nanogels were obtained through the double-crosslinking of chitosan with an ionic physical gelator and a disulfide-containing chemical crosslinker. After conjugation to an anionic oligomer, the cationic nanogels were transformed into negatively charged nanocarriers (CTCP), enabling effective encapsulation of the cationic anticancer agent doxorubicin (DOX) to generate a biodegradable nanomedicine (DOX@CTCP). DOX@CTCP could maintain sustained DOX release and decreased DOX toxicity. Upon arrival at the tumor tissue, the reductive and lysozyme-high microenvironment drives the cleavage of the nanomedicine to release DOX-carrying nanoblocks of smaller size, which together with their acidic-protonable feature achieves an effective therapeutic delivery into cancer cells. The nanomedicine described here showed excellent biocompatibility/biosafety and enhanced in vivo antitumor efficacy.
研究领域:
生物医学工程
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肿瘤学
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药剂学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
·
IF 3.887
Yuling Su,Lili Zhao,Fancui Meng,Quanxin Wang,Yongchao Yao,Jianbin Luo
In order to improve the antibacterial activities while decrease the cytotoxity of silver nanoparticles, we prepared a novel nanocomposites composed of silver nanoparticles decorated lipase-sensitive polyurethane micelles (PUM-Ag) with MPEG brush on the surface. The nanocomposite was characterized by UV–vis, TEM and DLS. UV–vis and TEM demonstrated the formation of silver nanoparticles on PU micelles and the nanoassembly remained intact without the presence of lipase. The silver nanoparticles were protected by the polymer matrix and PEG brush which show good cytocompatibility to HUVEC cells and low hemolysis. Moreover, at the presence of lipase, the polymer matrix of nanocomposites is subject to degradation and the small silver nanoparticles were released as is shown by DLS and TEM. The MIC and MBC studies showed an enhanced toxicity of the nanocomposites to both gram negative and gram positive bacteria, i.e. E. coli and S. aureus , as the result of the degradation of polymer matrix by bacterial lipase. Therefore, the nanocomposites are biocompatible to mammalian cells cells which can also lead to activated smaller silver nanoparticles release at the presence of bacteria and subsequently enhanced inhibition of bacteria growth. The satisfactory selectivity for bacteria compared to HUVEC and RBCs make PUM-Ag a promising antibacterial nanomedicine in biomedical field.
研究领域:
材料科学
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生物医学工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2017
·
IF 6.319
Huicong Zhou,Huanjiao Sun,Shixian Lv,Dawei Zhang,Xuefei Zhang,Zhaohui Tang,Xuesi Chen
Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue. Briefly, doxorubicin (DOX) was conjugated to carboxyl-terminated 4-arm poly(ethylene glycol) through a tetrapeptide linker, alanine-alanine-asparagine-leucine (AANL), which was one of the substrates of legumain , an asparaginyl endopeptidase that was found presented in plants, mammals and also highly expressed in human tumor tissues. Hereinafter, the polymer-DOX conjugate was termed as 4-arm PEG-AANL-DOX. Dynamic laser scattering (DLS) and transmission electron microscopy (TEM) measurements indicated that the 4-arm PEG-AANL-DOX could self-assemble into micelles in aqueous solution. Drug release and in vitro cytotoxicity studies revealed that the 4-arm PEG-AANL-DOX could be cleaved by legumain. Ex vivo DOX fluorescence imaging measurements demonstrated that the 4-arm PEG-AANL-DOX had an improved tumor-targeting delivery as compared with the free DOX·HCl. In vivo studies on nude mice bearing MDA-MB-435 tumors revealed that the 4-arm PEG-AANL-DOX had a comparable anticancer efficacy with the free DOX·HCl but without DOX-related toxicities to normal tissues as measured by body weight change and histological assessments, indicating that the 4-arm PEG-AANL-DOX had an improved therapeutic index for cancer therapy. Statement of Significance Herein we describe the construction of a novel tumor environment-sensitive delivery system through the instruction of a legumain-cleavable linkage to a polymer-DOX conjugate (4-arm PEG-AANL-DOX). This particular design strategy allows for polymer-DOX conjugates to be delivered in a tumor-specific manner and selectively activable in tumor microenvironment so that it can combine the advantages of tumor-specific delivery and tumor intracellular microenvironment-triggered release systems.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·Vol. 12
·期 45
·11696-11707
·
IF 6.1
Songyan Guo,Youbei Qiao,Chaoli Wang,Yuming Zhang,Tiehong Yang,Hong Wu
Nanoparticles (NPs) derived from branched copolymers of poly (β-L-malic acid) (PMLA) have been extensively investigated for drug delivery due to their high density of pendant carboxyl groups. This abundant functional group availability enhances their potential as effective drug delivery systems; however, the strong negative charge of PMLA poses a challenge in its uptake by cancer cells due to electrostatic repulsion. In this study, we developed novel enzyme- and pH-sensitive nanoparticles (EP-NPs) based on PMLA, demonstrating tumor-specific behavior and selective activation within tumor tissues. To enhance the cellular internalization of the nanoparticles, we incorporated transactivator of transcription (TAT). In summary, long-chain polyethylene glycol (PEG) was conjugated to PMLA to confer specificity to the TAT peptide. This was achieved using a tetrapeptide linker: alanine–alanine–asparagine–leucine (AANL), which serves as a substrate for legumain. Legumain is a highly conserved cysteine protease primarily found in lysosomes and blood vessels, initially discovered in legumes. It is markedly overexpressed in numerous solid tumors, as well as in endothelial cells and tumor-associated macrophages. The release of doxorubicin in tumor cells was sustained due to the low pH (5.0–5.5) and degradation of PMLA. The PEG modification optimized the particle size and shielded the nanoparticles from plasma proteins and detection by the reticuloendothelial system, thereby prolonging their long circulation time. Once the nanoparticles reached the tumor microenvironment, the AANL was cleaved by legumain, exposing the TAT peptide on the surface, which enhances cellular internalization. Both in vitro and in vivo efficacy studies demonstrated that these EP-NPs significantly inhibited tumor growth while exhibiting negligible systemic toxicity, thereby suggesting that the developed enzyme/pH-sensitive PMLA-based nanoparticle holds great promise as an anti-tumor drug delivery system.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 98
·80728-80738
·
IF 3.84
Chunyu Yang,Wei Guo,Na An,Liru Cui,Ting Zhang,Ruihan Tong,Yuhua Chen,Huiming Lin,Fengyu Qu
Fe3O4@mSiO2 (magnetic Fe3O4 core coated by a mesoporous silica shell) nanoparticles were successfully synthesized as a carrier. The anti-cancer drug doxorubicin (DOX) and chlorambucil (Chl) were used as the model cargo. After the drug-loading, a sodium hyaluronic acid (HA) cross-linked gel was adopted to coat the outside of the Fe3O4@mSiO2 nanoparticles as a layer (named as drug–Fe3O4@mSiO2–HA) to prevent drug pervasion. The detailed release kinetics were investigated, revealing the sensitive release triggered by hyaluronidase (HAase), a major enzyme which is rich in the tumor microenvironment, which can degrade the HA shell to induce the enzyme sensitive drug release. Moreover, there are some HA receptors in many tumor areas, associating with magnetic targets to further ensure the specific targeted drug delivery. With these improved performances, these smart multifunctional nanocomposites are expected to possess potential applications in the biopharmaceutical for cancer therapy.
研究领域:
生物医学工程
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药学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2014
·Vol. 5
·期 12
·9130-9137
·
IF 3.708
Jiahuan Lei,Yu Liu,Xinyu Wang,Pan Hu,Xinsheng Peng
Au nanoparticles/mesoporous CuO nanosheets were successfully synthesized by the assembly of negatively charged AuCl4−1 and positively charged CuO nanosheets using sodium citrate and thermal reduction, respectively. The structure and morphology were characterized in detail. Both the loading amount of Au nanoparticles and the performance were controlled by the reduction process. The resulting Au/CuO NSs exhibited good catalytic activity for CO oxidation and good non-enzymatic sensitivity for glucose.
研究领域:
材料科学
·
化学
·
生物传感
·
催化反应
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 6
·1010-1019
·
IF 0
Chunyu Yang,Wei Guo,Liru Cui,Na An,Ting Zhang,Gang Guo,Huiming Lin,Fengyu Qu
Multifunctional nanocarriers based on the magnetic Fe3O4 nanoparticle core and bis-(3-carboxy-4-hydroxy phenyl) disulfide (R–S–S–R1) modified mesoporous silica shell (Fe3O4@mSiO2@R–S–S–R1) were synthesized for cancer treatment through passive targeting and enzyme-sensitive drug release. Anti-cancer drug doxorubicin (DOX) was used as the model cargo to reveal the release behavior of the system. The drug loading system (DOX–Fe3O4@mSiO2@R–S–S–R1) retains the drug until it reaches the tumor tissue where glutathione reductase (GSH) can degrade the disulfide bonds and release the drug. Furthermore, the grafting amount of R–S–S–R1 can be used to adjust the release performance. All the release behaviors fit the Higuchi model very well and the release kinetics are predominated by disulfide bond degradation and mesoporous structure. With good bioactivity and targeted release performance, the system could play an important role in the development of intracellular delivery nanodevices for cancer therapy.
研究领域:
生物医学工程
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纳米医学
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肿瘤治疗
✓ 已验证
产品关联
DOI
PubMed
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Haijie Han,Jinhui Wang,Tingting Chen,Lichen Yin,Qiao Jin,Jian Ji
Development of gemcitabine (GEM) nanocarriers as theranostic agents for pancreatic cancer chemotherapy has received extensive attention in recent years. A novel enzyme-sensitive albumin-based GEM delivery nanoplatform was developed in this research by simple conjugation of GEM to human serum albumin (HSA) via cathepsin B cleavable peptide GFLG and then complexing with near-infrared (NIR) dye IR780, forming a HSA-GEM/IR780 complex. The successful preparation of HSA-GEM/IR780 complex was confirmed by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS), UV–vis–NIR absorption spectra and fluorescent emission spectra . The in vivo performance of HSA-GEM/IR780 complex was carried out on BxPC-3 pancreatic tumor xenografted mice. As revealed by in vivo NIR imaging, HSA-GEM/IR780 exhibited enhanced accumulation and long-term retention in tumor tissues compared to free IR780. Meanwhile, compared to free GEM, the deamination of GEM nanovectors into inactive 2′,2′-difluorodeoxyuridine (dFdU) can be greatly suppressed, while the concentration of the activated form of GEM (gemcitabine triphosphate, dFdCTP) was significantly increased in tumor tissue, thus exhibiting superior tumor inhibition activity with minimal side effects.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Liu Zhe,Zhou Dong,Liao Lan
The majority of current nanocarriers in cancer treatment fail to deliver encapsulated cargos to their final targets at therapeutic levels, which decreases the ultimate efficacy. In this work, a novel core–shell nanocarrier with a biodegradable property was synthesized for efficient drug release and subcellular organelle delivery. Initially, silver nanoparticles (AgNPs) were grafted with terminal double bonds originating from N, N′-bisacrylamide cystamine (BAC). Then, the outer coatings consisting of chitosan (CTS) and polyvinyl alcohol (PVA) were deposited on the surface of modified AgNPs using an emulsion method. To improve the stability, disulfide-containing BAC was simultaneously reintroduced to cross-link CTS. The as-prepared nanoparticles (CAB) possessed the desired colloidal stability and exhibited a high drug loading efficiency of cationic anticancer agent doxorubicin (DOX). Furthermore, CAB was tailored to transform their size into ultrasmall nanovehicles responding to weak acidity, high glutathione (GSH) levels, and overexpressed enzymes. The process of transformation was accompanied by sufficient DOX release from CAB. Due to the triple sensitivity, CAB enabled DOX to accumulate in the nucleus, leading to a great effect against malignant cells. In vivo assays demonstrated CAB loading DOX held excellent biosafety and superior antitumor capacity. Incorporating all the benefits, this proposed nanoplatform may provide valuable strategies for efficient drug delivery.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Debin Yang,Tingfang Wang,Zhigui Su,Lingjing Xue,Ran Mo,Can Zhang
A multistimuli responsive drug delivery system (DDS) based on sulfhydryl and amino-cofunctionalized mesoporous silica nanoparticles (SH/NH2-MSNs) has been developed, in which the multifunctional hyaluronic acid (HA) derivatives were grafted onto the SH/NH2-MSNs by disulfide bonds for targeting delivery, controlling drug release and reversing multidrug resistance (MDR). The doxorubicin (Dox) loaded multifunctional HA derivatives modified mesoporous silica nanoparticles (Dox/HHS-MSNs) were enzyme and redox sensitive, which could respond to the intracellular stimuli of hyaluronidase (HAase) and glutathione (GSH) successively and prevent drug leakage before reaching the tumor tissues. The cellular uptake experiments showed that Dox/HHS-MSNs were vulnerable to be endocytosed into the Dox-resistant human breast adenocarcinoma (MCF-7/ADR) cells, efficiently realized the endolysosomal escape and remained in the cytoplasm. Because of orchestrating multiple actions above including active targeting, endolysosomal escape and efficient multilevel drug release, Dox/HHS-MSNs could induce the strongest apoptosis and cytotoxicity of MCF-7/ADR cells. Furthermore, a series of in vivo studies on MCF-7/ADR tumor-bearing xenograft mouse models demonstrated that Dox/HHS-MSNs possessed the enhanced tumor-targeting capacity and the best therapeutic efficacy to reverse cancer MDR.
研究领域:
药学科学
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纳米技术
·
癌症研究
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Qibin Li,Quanyi Chen,Yueying Wu,Zhibao Chen,Ying Liu,Zhijia Fang,Qi Deng
The bacteriocin CAMT6 is a novel bacteriocin produced by Enterococcus durans YQ-6 isolated from Larimichthys polyactis in the South China Sea. In this study, the bacteriocin CAMT6 was purified by extraction using ethyl acetate, Sephadex LH-20 column chromatography, cation exchange chromatography and reversed-phase high-performance liquid chromatography, in sequence. The Liquid Chromatograph Triple Quadrupole Mass Spectrometer (LC-MS/MS) analysis revealed that the relative molecular mass and amino acid sequence of the bacteriocin CAMT6 were 1254.63 Da and N-GAVHDVKDVLDS, respectively. Combined with the circular dichroism (CD) spectroscopy results, CAMT6 was determined to be a novel Class IId bacteriocin. CAMT6 exhibited broad-spectrum antibacterial activity, inhibiting both gram-negative and gram-positive bacteria, even fungi. CAMT6 exhibited strong temperature stability, was stable over pH 2–7, and was inactivated by proteases. CAMT6 also significantly removed L. monocytogenes biofilms and inhibited L. monocytogenes by disrupting the permeability of the cell membrane. Furthermore, CAMT6 can effectively inhibit the growth of L. monocytogenes in chicken breast. These results suggest that the bacteriocin CAMT6 could serve as a potential biological preservative for food.
研究领域:
微生物学
·
食品科学
·
生物化学
✓ 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）