COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Pengcheng Liu,Qiong Wu,Yanmei Li,Pengfei Li,Jiang Yuan,Xianwei Meng,Yinghong Xiao
Keratin is a good candidate for drug carrier due to its good biocompatibility, low immunogenicity, redox responsiveness, and abundant renewable sources. Herein, doxorubicin (DOX) was first conjugated with keratin through a pH-sensitive hydrazone linkage, and then prepared into particulate drug carrier via desolvation method. The size, morphology, and surface potential of keratin-DOX nanoparticles (KDNPs) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug release results showed that KDNPs performed an excellent pH-sensitive behavior under acidic tumor microenvironment. Cytotoxicity assay by MTT confirmed that KDNPs exhibited the enhanced cytotoxicity against A549 cells. Furthermore, KDNPs had higher therapeutic efficiency in vivo than free DOX . Hemolysis assay indicated that KDNPs was blood compatible. All the results identified that KDNPs are well suited as an ideal drug carrier.
研究领域:
药剂学
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生物材料
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2016
·Vol. 18
·期 3
·749-758
·
IF 1.954
Sun Yujie,Zhang Jing,Han Jian,Tian Baocheng,Shi Yanan,Ding Yuanyuan,Wang Lele,Han Jingtian
A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl- D -galactopyranose) (mPEG- b -PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG- b -PMAGP- co -DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG- b -PMAGP- co -DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG- b -PMAGP- co -DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG- b -PMAGP- co -DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG- b -PMAGP- co -DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.
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
International Journal of Nanomedicine
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2023
·
IF 8
Lan Tang,Wenhui Jiang,Lan Wu,Xiaolan Yu,Zheng He,Weiguang Shan,Lulu Fu,Zhenhai Zhang,Yunchun Zhao
Background Doxorubicin (DOX) is an anthracycline antibiotic that inhibits the growth of several solid and hematologic malignant tumors. Increasing the targeting ability of DOX and reducing the multi-drug resistance (MDR) of tumor cells to DOX are major aims for researchers.Purpose In this study, to increase therapeutic efficiency, reduce the side effects and the MDR of tumor cells to DOX, D-alpha-tocopheryl polyethylene glycol 2000 succinate monoester (TPGS2000)-DOX prodrug micelles were developed by grafting DOX to TPGS2000 via an amide bond that release DOX in the slightly acidic conditions in tumor tissue.Materials and Methods The TPGS2000-DOX micelles were constructed using polyethylene glycol 12-hydroxy stearate (Solutol HS15) as the carrier. The in vitro drug release profile and dilution stability of the nanomicelles were determined. The in vitro cytotoxicity and distribution of the nanomicelles in the tumor cells were also investigated. Moreover, we explored the therapeutic outcomes using the MCF-7/ADR tumor-bearing murine model.Results The average particle size was approximately 30 nm with a narrow distribution, which was conducive for solid tumor accumulation. The results of in vivo imaging and in vitro cellular uptake assays demonstrated that the TPGS2000-DOX micelles increased the tumor-targeting ability and cellular uptake of DOX. The anticancer potential of TPGS2000-DOX micelles was higher than that of DOX, as revealed by in vitro cytotoxic assays with MCF-7/ADR cells and in vivo antitumor assays with MCF-7 tumor-bearing nude mice.Conclusion TPGS2000-DOX prodrug micelles reverse the MDR of tumor cells, achieve passive targeting by forming nanomicelles, and subsequently enhance the efficacy and reduce the toxicity of DOX.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
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2024
·
IF 2.8
Jiangtao Su,Xue Chen,Fan Ye,Chuchu Liu,Jiahao Liang,Xuejun Zhang,Xiaoxia Guo
Background: Multidrug resistance (MDR) is a key challenge in clinical chemotherapy. The combination of drugs can effectively reverse multi-drug resistance. Objective: In this study, doxorubicin (DOX) was capsulated into nanoparticles formed by an amphiphilic PEGylated-poly (α-lipoic acid)-methanamide analogue of celastrol (mPEG-PαLA-CEN) prodrug polymer. CEN was linked to the branched chain of poly (α-lipoic acid) by forming ester bonds. DOX was physically trapped inside the nanoparticles via electrostatic interaction. Both drugs can be simultaneously released in response to low pH and high GSH in order to overcome DOX resistance. Methods: The chemical structure of the mPEG-PαLA-CEN-DOX NPs was confirmed through 1H NMR, FT-IR spectroscopy, UV-Vis spectrum, DLS, and TEM. Drug-loading content, efficacy, and drug release were measured using HPLC. Cell toxicity was examined using an MTT assay. Results: CEN/DOX-loaded nanoparticles were found to have spherical shapes with diameters of around 229.7 nm. The NPs exhibited high biocompatibility and released 92% DOX and 71.8% CEN in response to low pH and high GSH of tumor microenvironments. As dual drug-loaded nanoparticles, the efficacy of mPEG-PαLA-CEN-DOX NPs against tumor cell lines in vitro was enhanced for both MCF-7 and MCF-7/ADR compared to free DOX. Compared to free DOX, the IC50 of mPEG-PαLA-CEN-DOX NPs reduced from 46.10 μM to 8.36 μM for the MCF-7/ADR cell line. Conclusion: In conclusion, this study demonstrated that PEGylated poly (α-lipoic acid)-CEN copolymers can be used not only as biocompatible, stimulation-responsive anticancer drug nanocarriers but also as chemosensitizers to overcome multidrug resistance, which provide a theoretical base for clinical application of CEN/DOX nanodrug.
研究领域:
肿瘤学
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药物递送
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纳米医学
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多药耐药逆转
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化学治疗
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2018
·
IF 4.556
Yuemin Wang,Xiaomei Chen,Dahua He,Yi Zhou,Linghao Qin
Anticancer drugs cannot be located in the tumor efficiently when intravenously administered because of their weak tissue specificity and often present the problems of low therapeutic activity and severe adverse effects. To conquer these challenges, a targeting nanomedicine system based on human body cells or cell derivates have drawn more attention from scientists in recent decades. In this work, we used doxorubicin (DOX) as a model drug and a nanoerythrocyte modified with folic acid (FA) and polyethylene glycol (PEG) as a carrier to develop a novel tumor targeting drug delivery system (FA/PEG–DOX–Nano-RBCs) to enhance antitumor efficacy and reduce drug-related toxicity. The results showed that this drug delivery system exhibited inspiring features including nanoscale particle size with uniform distribution, good physicochemical stability, and sustained drug release behavior. Compared with DOX injection, FA/PEG–DOX–Nano-RBCs can greatly prolong the drug circulation time in vivo and upgrade the drug concentration accumulated in tumor tissue. Moreover, FA/PEG–DOX–Nano-RBCs exerted stronger antitumor efficacy in vivo against liver cancer and showed superior safety. In conclusion, a surface-modified nanoerythrocyte was a promising drug delivery vehicle for achieving improved therapeutic efficacy and reduced systemic adverse effects for 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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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2015
·
IF 5.75
Xu Jia,Xubo Zhao,Kun Tian,Tingting Zhou,Jiagen Li,Ruinian Zhang,Peng Liu
A novel water-soluble pH stimuli-responsive fluorescent copolymer of P(PEGMA-b-(MAH-co-Rh6GEAm)) was synthesized by two-step sequential RAFT polymerization. The prodrug with drug content of 0.1560 mg/mg was prepared by coupling doxorubicin (DOX) onto the copolymer via acid-cleavable hydrazone bond, formed between the carbonyl group of DOX and abundant hydrazide functional groups in the copolymer. The amphiphilic DOX-conjugated prodrug (P(PEGMA-b-(MAH-DOX-co-Rh6GEAm))) could easily form a micelle in water with Dh of less than 100 nm. It could be transported into HepG2 cells and release DOX without burst release, while the leakage of DOX can be avoided in the simulated normal physiological media. Furthermore, its fluorescence intensity experienced a reversible change with the transformation of the media pH. The better biocompatibility, pH stimuli-responsiveness, and the strong fluorescence at low pH media make the nanoparticles a potential platform for the controlled release of anticarcinogens and real-time fluorescent imaging of tumor tissues.
研究领域:
生物材料
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药物递送
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
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2022
·
IF 5.122
He Ma,Xiaoming Zhang,Long Pang,Bing Yu,Hailin Cong,Youqing Shen
The high toxicity and side effects of drugs as well as the difficulty of tracking their trends and metabolism have always been the core difficulties of anticancer drugs. In this paper, doxorubicin (DOX) was used as therapeutic drug to coordinate with Mn 2+ to obtain the hydrophobic core of nanomedicine . The outer layer was self-assembled and coated with amphiphilic block copolymer-distearyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) to form [email protected] micellar nanoparticles (MDDM NPs) with good dispersion and stability. Cell experiments showed that MDDM micellar nanoparticles could be effectively uptaked by cells in a short time, and had good biocompatibility and tumor inhibition. In vivo experiments have shown that nanoparticles not only have excellent therapeutic effects, but also have magnetic resonance imaging contrast as contrast agents due to Mn 2+ coordination, which can assist in tracking drug trends and metabolism in vivo. The above work provides a certain reference significance for the study of combining organic drugs with metals to realize the reduction of drug toxicity and provide multimodal function of metals.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
·
分子成像
✓ 已验证
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2019
·Vol. 20
·期 2
·1900331
·
IF 2.895
Runhai Chen,Zhifang Ma,Zehong Xiang,Yu Xia,Qiang Shi,Shing-Chung Wong,Jinghua Yin
Polymer nanoparticulate drug delivery systems that respond to reactive oxygen species (ROS) and glutathione (GSH) simultaneously at biologically relevant levels hold great promise to improve the therapeutic efficacy to cancer cells with reduced side effects of chemo drugs. Herein, a novel redox dual-responsive amphiphilic block copolymer (ABP) that consists of a hydrophilic poly (ethylene oxide) block and a hydrophobic block bearing disulfide linked phenylboronic ester group as pendant is synthesized, and the DOX loaded nanoparticles (BSN-DOX) based on ABPs with varied hydrophobic block length are fabricated for DOX delivery. The self-immolative leaving reaction of phenylboronic ester triggered by extracellular ROS and the cleavage of disulfide linkages induced by intracellular GSH both lead to rapid DOX release from BSN-DOX, resulting in an on-demand DOX release. Moreover, BSN-DOX show better tumor inhibition and lower side effects in vivo compared with free drug.
研究领域:
药剂学
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2018
·Vol. 47
·期 7
·2435-2443
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IF 4.099
Yuhua Chen,Feng Zhang,Qian Wang,Huiming Lin,Ruihan Tong,Na An,Fengyu Qu
A facile methodology is presented to construct a multifunctional nanocomposite that integrates photothermal therapy and specific drug release into a single nanostructure. Firstly, magnetic Fe3O4@polydopamine core–shell nanoparticles (Fe3O4@PDA) were synthesized via a reversed-phase microemulsion approach. By varying the amount of DA, Fe3O4@PDA with a particle size of 28–38 nm can be obtained. To further ensure the monodispersity, biocompatibility and specific uptake, PEG and lactobionic acid (LA) were grafted onto Fe3O4@PDA (LA-Fe3O4@PDA-PEG), whose fast photothermal conversion is derived by the combination of Fe3O4 and PDA with high near infrared (NIR) absorption. Then, doxorubicin hydrochloride (DOX) was adopted as the typical anticancer drug, which was loaded onto LA-Fe3O4@PDA-PEG via electrostatic and π–π stacking interaction. The release kinetics investigation further demonstrated the acid/heat-triggered DOX release. HepG2 cells (hepatocellular cell line) were used as the target cancer cells, and the fast uptake was due to the nanoparticle size and abundant asialoglycoprotein receptors on HepG2 cells. Besides, an external magnetic field also can improve the uptake, especially when the magnet is placed at the bottom of the cell disk. The enhanced specific cytotoxicity toward HepG2 cells was also ascribed to the synergistic effect of chemo- and photothermal therapy. Based on the novel properties, the LA-Fe3O4@PDA-PEG-DOX nanocomposite showed its potential application in hepatocyte therapy.
研究领域:
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
BIOMACROMOLECULES
·
2017
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IF 5.246
Jia Tian,Lei Xu,Yudong Xue,Xiaoze Jiang,Weian Zhang
Drug resistance is a primary obstacle that seriously reduces the therapy efficiency of most chemotherapeutic agents. To address this issue, the photochemical internalization (PCI) was employed to help the anticancer drug escape from lysosome and improve their translocation to the nucleus. A pH-sensitive porphyrin-based amphiphilic block copolymer (PEG113-b-PCL54-a-porphyrin) was synthesized, which was acted not only as a carrier for the delivery of DOX but also as a photosensitizer for PCI. PEG113-b-PCL54-a-porphyrin as a drug carrier exhibited a higher drug loading capacity, entrapment efficiency, and DOX release content. The PCI effect of PEG113-b-PCL54-a-porphyrin was studied by confocal laser scanning microscopy, and the results showed that most of DOX could be translocated into the nucleus for DOX-loaded PEG113-b-PCL54-a-porphyrin micelles. Moreover, the IC50 of pH-sensitive DOX-loaded PEG113-b-PCL54-a-porphyrin micelles was much lower than that of its counterpart without pH-responsiveness, DOX-loaded PEG113-b-PCL54-porphyrin micelles. Therefore, this drug delivery system based on pH-sensitive porphyrin-containing block copolymer would act as a potential vehicle for overcoming drug resistance in chemotherapy.
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
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
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肿瘤学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
·
2023
·Vol. 129
·期 12
·877
·
IF 2.7
Ding Feng,Qiu Guobin,Tan Fengliang,Wu Tengyan,Ding Longzhen,Liu Xin,Zhong Hongbin
Characterization results of Fourier transformed infrared spectrometer(FT-IR), thermogravimetry–differential thermal analysis TG–DTA, dynamic stability control (DSC), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM) indicated that DOX loaded onto PEGylated superparamagnetic Mn 0.6 Zn 0.4 Gd 0.04 Fe 1.96 O 4 (MNPs) was prepared successfully. DOX loading ration and release mechanism was analyzed; the result indicated that the DOX loading ration increased with initial charge DOX increasing, and DOX release was a Fickian diffusion mechanism, with 34.5% of DOX released in PBS solution at 43 °C within 168 h. Consequently, the MNPs@PEG may be a good targeted drug delivery system for tumor targeted and hyperthermia MNPs as therapeutic applications.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）