INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
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IF 3.994
Lele Wang,Baocheng Tian,Jing Zhang,Keke Li,Yan Liang,Yujie Sun,Yuanyuan Ding,Jingtian Han
Multifunctional polymeric micelles self-assembled from a DOX-conjugated methoxypolyethylene glycols- b -poly (6- O -methacryloyl- d -galactopyranose)-disulfide bond-DOX (mPEG- b -PMAGP-SS-DOX) copolymer were prepared as an antitumor carrier for doxorubicin delivery, of which the chemical modification with disulfide bonds and hydrazone bonds allowed micelles to release doxorubicin (DOX) selectively at acidic pH and high redox conditions. The resulting micelles exhibited coordinated pH/redox dual-sensitive and hepatoma-targeted multifunction with sustaining stability in aqueous media. The multifunctional micelles showed spherical shapes with a mean diameter of 93 ± 2.08 nm, a low polydispersity index (PDI) of 0.21, a low CMC value of 0.095 mg/mL, a high drug grafting degree of 56.9% and a drug content of 39.0%. Remarkably, in vitro drug release studies clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release treated with pH 5.0 and 10 mM GSH (88.4% in 72 h) without drug burst release. The tumor proliferation assays indicated that DOX-grafted micelles, along with low cytotoxicity and well biocompatibility to normal cells up to a concentration of 10 μg/mL, inhibited the proliferation of HepG2 cells in a formulation-, time- and concentration-dependent manner in comparison with MCF-7 cells which was similar to free DOX. Anticancer activity releaved that the disulfide-modified micelles possessed much higher anti-hepatoma activity with a low IC 50 value of 1.1 μg/mL following a 72 h incubation. Furthermore, the intracellular uptake tested by CLSM and FCM demonstrated that multifunctional polymeric micelles could be more efficiently taken up by HepG2 cells compared with MCF-7 cells, agreed well with MTT assays, suggesting these well-defined micelles provide a potential drug delivery system for dual-responsive controlled drug release and enhanced anti-hepatoma therapy.
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Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Aili Suo,Junmin Qian,Minghui Xu,Weijun Xu,Yaping Zhang,Yu Yao
Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanovehicle has emerged as a promising combination therapy approach to treating cancers because of their synergistic effect. Nanocarrier delivery systems with low cytotoxicity and high efficiency are needed for such a purpose. In this study, a novel folate-conjugated PEGylated cationic triblock copolymer, poly(acrylhydrazine)- block -poly(3-dimethylaminopropyl methacrylamide)- block -poly(acrylhydrazine) (PAH- b -PDMAPMA- b -PAH), was synthesized and evaluated as a stimuli-sensitive vehicle for the targeted co-delivery of doxorubicin (DOX) and Bcl-2 siRNA into breast cancer MCF-7 cells. The synthetic process of the PEGylated triblock copolymer involved sequential reversible addition-fragmentation chain transfer polymerization, PEGylation and removal of tert -butoxy carbamate protecting groups. Folate-conjugated and/or -unconjugated poly(ethylene glycol) segments were grafted onto PAH- b -PDMAPMA- b -PAH via a reduction-sensitive disulfide linkage. The synthetic polymers were characterized by 1 H NMR and gel permeation chromatography. The PEGylated triblock copolymer could chemically conjugate DOX onto PAH blocks via pH-responsive hydrazone bonds and simultaneously complex negatively charged Bcl-2 siRNA with cationic PDMAPMA blocks through electrostatic interactions at N/P ratios ≥ 32:1 to form multifunctional nanomicelleplexes. The nanomicelleplexes exhibited spherical shape, possessed a positively charged surface with a zeta potential of + 22.5 mV and had a desirable and uniform particle size of 187 nm. In vitro release studies revealed that the nanomicelleplexes could release DOX and Bcl-2 siRNA in a reduction and pH dual-sensitive manner and the payload release was significantly enhanced in a reductive acidic environment mimicking the endosomes/lysosomes of cancer cells compared to under physiology conditions. Furthermore, the release of both DOX and siRNA was found to follow Higuchi kinetic model. Confocal laser scanning microscopy, flow cytometry and MTT analyses confirmed that, compared with folate-undecorated nanomicelleplexes, folate-decorated nanomicelleplexes could more effectively co-deliver DOX and Bcl-2 siRNA into MCF-7 cells and showed a stronger cell-killing effect. The pristine PEGylated triblock copolymer exhibited good cytocompatibility. Moreover, co-delivery of DOX and Bcl-2 siRNA achieved a significant synergistic antitumor efficacy. These findings suggested that the folate-decorated PEGylated cationic triblock copolymer might be a promising vehicle for targeted intracellular co-delivery of DOX and siRNA in MCF-7 cells, representing a potential clinical combination therapy for breast cancer treatment.
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ACS Applied Bio Materials
·
2021
·
IF 0
Ying Lu,Yizao Wan,Deqiang Gan,Quanchao Zhang,Honglin Luo,Xiaoyan Deng,Zhen Li,Zhiwei Yang
Simultaneous prevention of bone tumor recurrence and promotion of repairing bone defects resulting from tumorectomy remain a challenge. Herein, we report a polydopamine (PDA)-coated composite scaffold consisting of doxorubicin (DOX)-loaded lamellar hydroxyapatite (LHAp) and poly(lactic-co-glycolic acid) (PLGA) in an attempt to reach dual functions of tumor inhibition and bone repair. The DOX was intercalated into LHAp, and the DOX-loaded LHAp was incorporated into PLGA solution to prepare a DOX-intercalated LHAp/PLGA (labeled as DH/PLGA) scaffold that was coated with PDA to obtain a PDA@DH/PLGA scaffold. The morphology, structure, wettability, mechanical properties, drug release, biocompatibility, and in vitro and in vivo bioactivities of the PDA@DH/PLGA scaffold were evaluated. It is found that PDA coating not only improves hydrophilicity and mechanical properties, but also leads to more sustainable drug release. More importantly, the PDA@DH/PLGA scaffold shows significantly inhibited growth of tumor cells initially and subsequent improved adhesion and proliferation of osteoblasts. In addition, the PDA coating improves the bioactivity of the DH/PLGA scaffold as suggested by the in vitro biomineralization. Further in vivo study demonstrates the improved bone growth around PDA@DH/PLGA over DH/PLGA after 20 days of drug release. The dual functional PDA@DH/PLGA scaffold shows great promise in the treatment of bone tumor.
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APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Congyue Zhao,Chunling Li,Minghui Chen,Tianqi Niu,Qian Zhao,Tianjun Ni,Dong Yan,Weidong Wu,Dong Liu
The exploitation of an efficient way to treat antineoplastic doxorubicin hydrochloride (DOX) is critical due to its harmful effects on the ecological system and human health. Recently, photocatalysis has emerged as one of the most feasible strategies to resolve this crisis. However, the development of novel catalysts with highly efficient photocatalytic activity still remains a great challenge. Herein, a novel 0D/3D Nb 2 O 5 QDs/C-doped g-C 3 N 4 type-II heterojunction with outstanding adsorption and photocatalytic degradation capacities for DOX was developed based on combining elemental doping, morphological design and heterojunction fabrication. The C-doping significantly promotes the visible light response and charge migration of g-C 3 N 4 , thus benefiting to the removal of DOX. Meanwhile, the 0D/3D heterogeneous morphology endows the catalysts with abundant active sites, high adsorptive capacity, favourable structural stability, high surface area and enhanced charge migration, which all contribute to the excellent adsorption and photocatalytic performance. The superoxide radicals shown a prominent role in the photocatalytic reaction. In addition, the Toxicity Estimation Software Tool, liquid chromatography-mass spectrometry and density functional theory calculations were also employed to investigate the DOX degradation mechanism, possible pathways and corresponding toxicity of intermediates. This work provides a promising way to develop highly efficient catalysts for the degradation of DOX.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2015
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IF 2.979
Xiupei Yang,Huanhuan Gao,Fan Qian,Chuan Zhao,Xiangjun Liao
An internal standard method has been developed for the simultaneous determination of anthracycline antibiotics, doxorubicin (DOX) and daunorubicin (DAN), in rabbit plasma using capillary electrophoresis (CE) with in-column double optical-fiber LED-induced fluorescence detection (CE-ICDOF-LED-FLD). Rhodamine B (RhB) was selected as an internal standard because its emission wavelength is similar to that of the anthracycline antibiotics. Parameters including buffer pH, buffer concentration, organic solvents and separation voltage have been investigated to explore the sensitivity and separation efficiency of DOX and DAN. The optimal electrophoretic separation conditions were a borate buffer (15 mM, pH 9.0) containing 50% acetonitrile (v/v), 10 s hydrodynamic injection at a height of 20 cm and a separation voltage of 15 kV. The developed CE-ICDOF-LED-FLD method provides limits of detection of 18 and 13 ng/mL for DOX and DAN in rabbit plasma samples, respectively. The recoveries ranging from 93.7 to 104.8% and the relative standard deviations at 1.1–1.7% were achieved for DOX and DAN in spiked rabbit plasma samples.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
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IF 3.902
Tingsheng Yan,Dalong Li,Jiwei Li,Feng Cheng,Jinju Cheng,Yudong Huang,Jinmei He
A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110 nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro . In simulated body fluid with 10 mM glutathione, the release rate in 12 h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2026
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IF 5
Yanzhi Wang,Lu Li,Yanting Fan,Jiaxin Zheng,Hongmin Liu
Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options and poor prognosis. Although doxorubicin (DOX)-loaded liposomes are clinically used, their tumor-targeting efficiency and overall therapeutic efficacy remain suboptimal. To overcome these limitations, we designed and synthesized a novel cationic lipid excipient, cholesterol–butyl–biguanide (CBB), and formulated DOX-loaded CBB liposomes (Lip CBB@DOX) via active loading. Physicochemical characterization confirmed well-defined vesicular morphology, a positive surface charge, and pH-responsive drug release. In vitro, Lip CBB@DOX markedly increased DOX uptake by 4T1 cells, leading to enhanced cytotoxicity, reduced migration and proliferation, and elevated apoptosis. Mechanistic studies showed that Lip CBB@DOX potentiated DOX-induced immunogenic cell death, as indicated by increased calreticulin exposure and HMGB1 release. In a 4T1 murine model, Lip CBB@DOX produced the greatest tumor growth inhibition without aggravating systemic toxicity; histology revealed reduced tumor-associated extramedullary hematopoiesis and extensive tumor necrosis. Collectively, these results indicate that CBB is a safe and effective liposomal excipient that enhances DOX delivery and amplifies ICD-mediated antitumor immunity, offering a promising strategy to improve TNBC therapy and informing future optimization of biguanide-modified liposomal carriers. Download: Download high-res image (163KB) Download: Download full-size image
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International Journal of Nanomedicine
·
2023
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IF 8
Xiao Liang,Yudi Wang,Hui Shi,Mengmeng Dong,Haobo Han,Quanshun Li
Background Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.
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高影响因子
MOLECULES
·
2022
·Vol. 27
·期 24
·8640
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IF 4.927
Ning Lv,Xun Qiu,Qianqian Han,Fengna Xi,Yina Wang,Jun Chen
A disposable and portable electrochemical sensor was fabricated by integrating vertically-ordered silica mesoporous films (VMSF) and electrochemically reduced graphene (ErGO) on a screen-printed carbon electrode (SPCE). Such VMSF/ErGO/SPCEs could be prepared by a simple and controllable electrochemical method. Stable growth of VMSF on SPCE could be accomplished by the introduction of an adhesive ErGO nanolayer owing to its oxygen-containing groups and two-dimensional (2D) planar structure. An outer VMSF layer acting as a protective coating is able to prevent the leakage of the inner ErGO layer from the SPCE surface. Thanks to the electrostatic permselectivity and anti-fouling capacity of VMSF and to the good electroactive activity of ErGO, binary nanocomposites of VMSF and ErGO endow the SPCE with excellent analytical performance, which could be used to quantitatively detect doxorubicin (DOX) in biological samples (human serum and urine) with high sensitivity, good long-term stability, and low sample amounts.Keywords:silica nanochannel array;electrochemically reduced graphene oxide;screen-printed carbon electrode;doxorubicin;electrochemical sensor
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ACS Nano
·
2023
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IF 17.1
Hongrui Zhu,Chenqi Huang,Jingran Di,Zepu Chang,Ke Li,Shuo Zhang,Xueping Li,Daocheng Wu
To achieve the maximum therapeutic effects and minimize adverse effects of trimodal synergistic tumor therapies, a cost-effective programmed photothermal (PTT)-chemodynamic (CDT)-coordinated dual drug chemotherapy (CT) trimodal synergistic therapy strategy in chronological order is proposed. According to the status or volumes of the tumors, the intensity and time of each therapeutic modality are optimized, and three modalities are combined programmatically and work in chronological order. The optimal synergistic therapy begins with high-intensity PTT for 10 min to ablate larger tumors, followed by medium-intensity CDT for several hours to eliminate medium-sized tumors, and then low-intensity coordinated dual drugs CT lasts over 48 h to clear smaller residual tumors. Composite nanoparticles, made of Fe-coordinated polydopamine mixed with copper peroxide as the cores and their surface dotted with lots of doxorubicin-Fe(III)-gossypol infinite coordination polymers (ICPs), have been developed to implement the strategy. These composite nanoparticles show excellent synergistic effects with the minimum dose of therapeutic agents and result in nearly 100% tumor inhibition for mice bearing PC-3 tumors and no observed recurrence within 60 days of treatment. The ratios of the different therapeutic agents in the composite nanoparticles can be adjusted to accommodate different types of tumors with this cost-effective programmed trimodal therapy strategy.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2016
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IF 3.773
XiuLing Xu,JingJing Li,ShunPing Han,ChengHao Tao,Luo Fang,Yue Sun,JiaZhen Zhu,ZeHua Liang,FanZhu Li
Effective targeting drug delivery system for glioma treatment is still greatly challenged by the existence of the blood–brain barrier (BBB) and the intracranial overspreading of anti-tumor drug. Herein, we presented a dual-functional glioma targeting delivery of doxorubicin based on the PAMAM G5 dendrimer , modified with folic acid (FA) to target tumor cell, also borneol (BO), a well known safe material derived from traditional Chinese medicine , to facilitate the BBB permeability and reduce the toxicity of naked PAMAM. The intracranial transportation and glioma targeting ability were evaluated on the BBB model and C6 glioma cells in vitro . Also, pharmacokinetics and biodistribution were studied on C6 glioma-bearing rats in vivo . It indeed reduced the cytotoxicity of PAMAM against both HBMEC and C6 cells by coupling BO on the surface, while efficiently boosted BBB permeability with the improvement of transportation ratio by 2 folds to the BO-unmodified conjugates. Furthermore, conjugated FA increased total uptake amount by C6 cells leading to strong inhibition with the 3-fold lower IC 50 value than FA-unmodified DOX conjugate. In comparison with DOX solution, FA-BO-PAMAM/DOX exhibited significantly prolonged half-life time and increased area under the curve and improved DOX accumulation in brain tumor. The tumor growth inhibition, in vivo , was significantly increased up to 57.4%. The median survival time of xenograft rats after administering FA-BO-PAMAM/DOX (28 days) was significantly prolonged compared to free DOX (18 days, P < 0.05) or other controls. In conclusion, this strategy of novel targeting nanocarrier provides a promising method to increase the drug accumulation in the tumor site for therapy of glioma.
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高影响因子
Acta Biomaterialia
·
2017
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IF 6.319
Yanna Yu,Zhipeng Zhang,Yun Wang,Hao Zhu,Fangzhou Li,Yuanyuan Shen,Shengrong Guo
It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39 °C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. This nano-sized system was constructed by filling the interior of AuNCs with DOX, ICG and 1-tetradecanol, and modifying the surface with biotinylated poly (ethylene glycol) via Au-S bonds, termed as DOX/ICG@biotin-PEG-AuNC-PCM. The DOX and ICG co-release from DOX/ICG@biotin-PEG-AuNC-PCM was much faster in PBS at 40 °C or under 808 nm NIR irradiation at 2.5 W/cm 2 than at 37 °C (e.g. 67.27% or 80.31% vs. 5.57% of DOX, 76.08% vs. 3.83% of ICG for 20 min). The flow cytometry and confocal laser scanning microscopy (CLSM) results showed, the AuNCs were taken up by MCF-7/ADR cells via endocytosis , thus enhancing DOX uptake; the biotin on AuNCs facilitated this endocytosis; NIR irradiation caused the heating of the AuNCs, triggering the DOX and ICG co-release and enhancing the distribution of DOX in nuclei, the released ICG generated ROS to take photodynamic therapy. Due to the above unique properties, DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC 50 against MCF-7/ADR cells was very low, only 0.48 µg/mL, much smaller than that of free DOX (74.51 μg/mL). Statement of Significance A new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39 °C, was prepared, termed as DOX/ICG@biotin-PEG-AuNC-PCM, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells. DOX/ICG@biotin-PEG-AuNC-PCM exerted excellent anti-tumor effects under NIR irradiation, its IC 50 against MCF-7/ADR cells was very low, only 0.48 µg/mL, much smaller than that of free DOX (74.51 μg/mL).
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