Journal of Nanomaterials
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2018
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IF 2.207
Kun Wang,Shouju Wang,Kun Chen,Yijing Zhao,Xingqun Ma,Lin Wang
Anaplastic thyroid cancer (ATC) is highly aggressive and tends to develop drug resistance to standard chemotherapies. To overcome the drug resistance of ATC, we synthesized dopamine-melanin nanoparticles (MNPs) loaded with doxorubicin (Dox) molecules. The Dox-loaded MNPs (Dox-MNPs) developed exhibited increased cellular uptake and enhanced therapeutic efficacy in drug-resistant ATC cell line HTh74R, compared with free Dox. The native MNPs were found to have excellent biocompatibility, which suggests that Dox-MNPs may have potential in the treatment of ATC.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Ying Wang,Feng Bai,Qiang Luo,Mingliang Wu,Gang Song,Hongmei Zhang,Jian Cao,Yanqing Wang
Lycium barbarum polysaccharide-doxorubicin (LBP-DOX) nanoparticles were synthesized via a one-step Schiff base reaction between oxidized Lycium barbarum polysaccharide (oxidized LBP) and doxorubicin (DOX). The structure of LBP-DOX nanoparticles was characterized by multi-spectral methods, 1 H nuclear magnetic resonance ( 1 H NMR), transmission electron microscopy (TEM), and thermo gravimetric analysis (TGA). The rheological properties of LBP-DOX nanoparticles were studied. With the increase of shear rate, the viscosity of LBP and LBP-DOX nanoparticles gradually decreases at 25 °C. Under the same strain, the storage modulus (G′) and loss modulus (G″) of LBP-DOX nanoparticles were inferior to LBP. The DOX release from LBP-DOX nanoparticles was pH-dependent and was accelerated by decreasing pH. Cytotoxicity study showed that the LBP-DOX nanoparticles have significantly enhanced cytotoxicity in vitro, especially for human Hepatic cancer cell line HepG2.
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Biomaterials Science
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2018
·Vol. 6
·期 9
·2527-2540
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IF 5.831
Hui Xiong,Jiang Ni,Zhijie Jiang,Fengchun Tian,Jianping Zhou,Jing Yao
Drug efflux induced by multidrug resistance (MDR) overexpression, as well as secondary drug resistance caused by subtoxic drug microenvironments as a result of inefficient drug release of nanoscopic drug carriers in tumor cells, are major bottlenecks for chemotherapy. In order to overcome these limitations, we have devised a synergism-based polymer supramolecular nanoassembly (LH) by combining hyaluronic acid (HA) modified curcumin (HA-CUR) with a pH-sensitive low molecular weight heparin (LMWH) derivative modified doxorubicin (L-DOX). Our study proved that HA modification not only facilitated tumor targeting drug delivery efficiency through CD44 receptors-mediated active tumor-targeting strategy but also significantly enhanced the MDR reversion effect of CUR by improving its biological stability in different physiological environments. Also, the L-DOX in LH could trigger rapid and effective DOX release under a varied pH value environment, thereby overcoming secondary drug resistance. More importantly, a synergistic antitumor effect was achieved by optimizing the ratio of HA-CUR and L-DOX in LH. Furthermore, LH showed a superior therapeutic effect over free DOX in two mouse models of human cancer. Taken together, these results demonstrated that LH might serve as an efficient platform for delivery of therapeutic payloads to overcome MDR.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2018
·Vol. 18
·期 7
·4464-4470
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IF 1.354
Ji Fan,Zhang Kun,Li Jie,Gu Yuanliang,Zhao Jinshun,Zhang Jianfeng
Cancer chemotherapy has limitations such as nonselective distribution of drugs, detrimental side effects on normal tissues; here we reported a smart pH and magnetic sensitive drug delivery system (DDS) based on PEGylated Fe3O4 superparamagnetic nanoparticles. The
citric-coated Fe3O4 (CIO) nanoparticles were firstly synthesized and further functionalized by biocompatible poly(ethylene glycol) bis(carboxymethyl ether) (COOH-PEG-COOH), thus PEGylated CIO (GCIO) nanoparticles were obtained. Doxorubicin (DOX) was conjugated as a model
drug to the nanoparticles via hydrazone bond. The roughly sphere GCIO nanoparticles were comparatively strong magnetism with high drug loading capability (~89%) in relatively uniform size. Drug release study revealed that the GCIO-DOX performed pH-responsive drug-release properties. MTT assay
demonstrated that GCIO nanoparticles possessed low cytotoxicity and good physiological stability. Further, cell viability results indicated that the GCIO-DOX showed effective cytotoxicity only a bit lower than free DOX. All obtained data indicated that the combined pH-responsive and magnetic
multifunction drug delivery system can has excellent potential applications in cancer therapy.
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ACS Biomaterials Science & Engineering
·
2018
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IF 4.432
Guoqing Ma,Jie Liu,Jinlin He,Mingzu Zhang,Peihong Ni
The development of novel stimuli-responsive and biodegradable polyphosphoester-anticancer prodrugs is of importance in designing water-soluble prodrugs utilized in the field of drug delivery. In this study, the focus is on the synthesis of biocompatible and biodegradable diselenide-containing polyphosphoester [PEEP-b-PBYP-Se]2 using reduction-responsive di(1-hydroxylundecyl) diselenide as an initiator to polymerize 2-(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane (BYP) and 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EOP). After that, a doxorubicin (DOX) derivative containing an azide group was linked onto the side chain of [PEEP-b-PBYP-Se]2 via the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction to yield a pH/reduction-responsive polymeric prodrug, namely [PEEP-b-(PBYP-hyd-DOX)-Se]2. The chemical structures of various polymers were characterized by nuclear magnetic resonance spectroscopy, ultraviolet–visible spectrophotometer, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. The self-assembly behavior measured by dynamic light scattering and transmission electron microscopy clearly supported the formation of the prodrug nanoparticles (NPs). The results indicated that the polymeric prodrug NPs were relatively uniform spheres that could maintain stability in a physiological condition but be cleaved in acidic or reductive medium. Furthermore, the pH- and reduction-responsive properties of the prodrug NPs were investigated via drug release in vitro in different media. It turned out that the drug was efficiently released in acidic or reductive medium compared with that under physiological conditions. The results of methyl thiazolyl tetrazolium assays confirmed the favorable biocompatibility of [PEEP-b-PBYP-Se]2. Moreover, the cell cytotoxicity and intracellular uptake experiments were carried out to verify the efficient cellular proliferation inhibition. This finding contributes to the design of a novel diselenide-containing polyphosphoester-doxorubicin prodrug.
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Nano Research
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2018
·Vol. 11
·期 6
·3396-3410
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IF 7.994
Wu Dongyan,Wang Huaisong,Hou Xiaoshuang,Chen Huan,Ma Yu,Hou Yanglong,Hong Jin,Ding Ya
Studies on the influence of one critical parameter (e.g., size), targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design of biomedical nanomaterials. In this study, we used doxorubicin (Dox)-conjugated gold nanoparticles (GNPs) to investigate the effects of the size of the gold core (10, 20, or 60 nm) on the performance of their conjugates. We found that all three conjugates differed slightly in their physicochemical properties, facilitating a direct and accurate assessment of the size effects of GNP-Dox conjugates on their in vitro and in vivo performance. The cytological properties (the cell penetration rate and efficiency, as well as the cytotoxicity) and antitumor performance (the intratumoral penetration, treatment efficacy, and biodistribution) were highly correlated to the size of the inorganic core. Among all test groups, although the conjugate with a 60-nm gold core had the highest drug loading and release efficiency, the conjugate with a 10-nm gold core displayed the best antitumor efficacy toward the liver cancer models. This was because it showed the deepest tumor permeability and the highest tumor cell-killing ability of Dox transported by the relatively small GNPs. This study provides important evidence for better understanding the effect of size on in vitro and in vivo properties of potential therapeutic nanosystems and their structure design.
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CELL PROLIFERATION
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2018
·Vol. 51
·期 5
·e12488
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IF 4.936
Tingting Kong,Liying Hao,Yuanyuan Wei,Xiaoxiao Cai,Bofeng Zhu
Objectives Carbon dots (CDs) are one of the most promising carbon-based materials in bioimaging and drug/gene delivery applications. In this study, we have attempted to study the drug carrying capacity of highly fluorescent CDs for delivery of doxorubicin (DOX) and investigate the therapeutic activity of the CDs-DOX drug delivery system. Materials and methods Carbon dots were synthesized by means of a hydrothermal approach with mixing citric acid and ethylenediamine. The properties of CDs were characterized in respects of spectral property, zeta potential, particle morphology and chemical composition. The drug loading efficiency (DLE) and release profile of CDs-DOX were determined by a fluorescence spectrophotometer. We investigated the cellular toxicity and pharmaceutical activity of CDs and CDs-DOX in L929 cells and MCF-7 cells by the CCK-8 assay. We also studied the cellular uptake of CDs-DOX with the methods of confocal microscopy and flow cytometry. In addition, the effect of CDs-DOX on cell apoptosis was assessed by flow cytometry. Results The obtained CDs possessed good biocompatibility and showed a potential capacity of promoting proliferation. DOX was successfully conjugated to CDs through electrostatic interaction, and the results of the DLE and loading content (DLC) suggested a relatively high drug loading capacity of CDs. Compared with free DOX, the CDs-DOX complex had a higher cellular uptake and better anti-tumour efficacy on MCF-7 cells. Conclusions The results of this study indicated that the CDs-DOX drug delivery system had a potential value in cancer chemotherapeutic application.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2019
·Vol. 19
·期 9
·5463-5468
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IF 1.093
Zhang Nan,Liu Xinyang,Hou Ruirui,Zhang Jiangnan,Li Jia,Huo Pengchao,Xu Yue,Zhang Zhenzhong
The purpose of current research is to develop ultrasound-triggered gas-generating Doxorubicin PLGA nanoparticle for cancer therapy. Method: pH-sensitive PLGA nanoparticles (PLGANPs) was fabricated to deliver doxorubicin (DOX) and sodium bicarbonate (NaHCO3) using the water-in-oil-in-water
(w/o/w) double emulsion method. Result: The nanoparticle with the size (650 nm) and high drug loading (15.8±2.3%) were successfully prepared and showed pH-responsive release characteristics. In vitro results indicate that DOX/NaHCO3@PLGANPs with ultrasound had higher
inhibition and cell uptake on MCF-7 cells than free DOX and other formulation. In vivo animal experiments showed that after treatment of DOX/NaHCO3@PLGANPs with ultrasound, the relative tumor volume (0.63) of S180-tumor-bearing mice was lower than that of without ultrasound
(0.81), DOX@PLGANPs (1.00) and Free DOX (1.12). Moreover, safety evaluation result indicated that DOX/NaHCO3@PLGANPs was safer than free DOX. In conclusion, the DOX/NaHCO3@PLGANPs was successfully developed and evaluated In vitro and In vivo. This drug delivery
system will be a promising strategy for cancer therapy and diagnosis.
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Biomaterials Science
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2019
·Vol. 7
·期 11
·4615-4623
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IF 5.251
Ting Xue,Caina Xu,Yu Wang,Yanbing Wang,Huayu Tian,Yingchao Zhang
Doxorubicin (DOX) as a traditional chemotherapy drug is restricted in clinical applications due to its poor therapeutic activity and severe side effects. Herein, we prepared a metal–organic framework (MOF) MIL-100 by a microwave-assisted synthesis and DOX was loaded in MIL-100 and then, hyaluronic acid (HA) was modified on the surface of MIL-100 to give DMH NPs. The DMH NPs possessed the following advantages: (1) MIL-100 could serve as a drug carrier with a high DOX loading efficiency; MIL-100 could also generate a hydroxyl radical (˙OH) in the presence of H2O2 for chemodynamic therapy (CDT) via a Fenton-like reaction. (2) To improve the dispersibility of MIL-100, HA was modified on the surface of MIL-100, which could endow MIL-100 with a targeting ability towards tumor tissues. (3) DMH NPs could enhance antitumor efficacy and reduce drug-related toxicity though the combination of chemotherapy and chemodynamic therapy. DMH NPs have enormous potential as a candidate for reducing the systemic toxicity and improving the treatment effect for breast cancer.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2017
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IF 4.159
Qian Xie,Wenji Deng,Xue Yuan,Huan Wang,Zhiguo Ma,Baojian Wu,Xingwang Zhang
Liposomes have shown to be an excellent drug delivery system , but the short in vivo fate discourages their popularity. This work aimed to develop selenium-functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the systemic circulation of liposomes by in situ selenium coating and enhance the anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox-SeLPs) were prepared by film hydration/active loading/ in situ reduction technique and characterized by particle size, entrapment efficiency and morphology. The resulting Dox-SeLPs were 127 nm around in particle size (uncoated liposomes 107 nm) and were spherical in morphology. It was shown that Dox-SeLPs possessed a sustained release effect for Dox and could increase the cellular uptake of Dox compared with Dox-loaded liposomes (Dox-LPs). The accumulative Dox release from Dox-SeLPs was 46.5% and it was 64.9% for Dox-LPs within 84 h. Moreover, Dox-SeLPs exhibited slower drug release in the fetal bovine serum. Trafficking pathway study revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the cellular uptake process of Dox-SeLPs. The in vitro cytotoxicity and apoptosis test indicated that Dox-SeLPs had higher cytotoxicity than that of free Dox and Dox-LPs. Dox-SeLPs showed a IC 50 of 0.92 ± 0.16 μg/mL on A549 cells, far lower than that of free Dox (4.40 ± 0.58 μg/mL) and Dox-LPs (5.68 ± 0.73 μg/mL). Dox-SeLPs significantly improved the pharmacokinetic property and enhanced the antitumor efficacy of Dox in tumor-bearing mice. In conclusion, SeLPs exhibit good sustained release for Dox and have synergic anticancer effect with Dox, which may be promising as drug delivery vehicle .
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SUPRAMOLECULAR CHEMISTRY
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2024
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IF 2.1
Caixia Li,Qin Zhou,Haoliang Huang,Liang Li
In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.
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BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
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2016
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IF 3.687
Yinghuan Li,Lei Gao,Xi Tan,Feiyang Li,Ming Zhao,Shiqi Peng
The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts ( B ) into saturable binding ( SB ) and nonsaturable binding ( NSB ) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e. , cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40 mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20 mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.
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