JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-11
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IF 9.429
Chen Mo,Qiao Yingyu,Cao Jie,Ta La,Ci Tianyuan,Ke Xue
Background Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in the bone marrow.Results Here, a biomimetic nanosystem (DR@PLip) based on platelet membrane (PM) coating and doxorubicin (DOX)/ginsenoside (Rg3) co-loading was developed to potentiate the local-to-systemic chemoimmunotherapy for AML. The PM was designed for long-term circulation and better leukemia cells targeting. The participation of Rg3 was proved to enhance the tumor sensitivity to DOX, thus initiating the anti-tumor immune activation and effectively combating the leukemia cells hiding in the bone marrow.Conclusion sIn conclusion, the strategy that combining immediate chemotherapy with long-term immunotherapy achieved improved therapeutic efficiency and prolonged survival, which provided a new perspective for the clinical treatment of AML.
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ACS Nano
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2022
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IF 18.027
Lan Yang,Yongshun Zhang,Yu Zhang,Yani Xu,Yuai Li,Zhiqiang Xie,Hairui Wang,Yunzhu Lin,Qing Lin,Tao Gong,Xun Sun,Zhirong Zhang,Ling Zhang
Triple-negative breast cancer is often aggressive and resistant to various cancer therapies, especially corresponding targeted drugs. It is shown that targeted delivery of chemotherapeutic drugs to tumor sites could enhance treatment outcome against triple-negative breast cancer. In this study, we exploited the active tumor-targeting capability of macrophages by loading doxorubicin-carrying liposomes on their surfaces via biotin–avidin interactions. Compared with conventional liposomes, this macrophage–liposome (MA-Lip) system further increased doxorubicin accumulation in tumor sites, penetrated deeper into tumor tissue, and enhanced antitumor immune response. As a result, the MA-Lip system significantly lengthened the survival rate of 4T1 cell-bearing mice with low toxicity. Besides, the MA-Lip system used highly biocompatible and widely approved materials, which ensured its long-term safety. This study provides a system for triple-negative breast cancer treatment and offers another macrophage-based strategy for tumor delivery.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Dao-Qiang Lu,Dahai Liu,Justin Liu,Wen-Xing Li,Yilong Ai,Jun Wang,Daogang Guan
Chitosan-based nanogels are effective carriers for drug delivery due to their biocompatibility and biodegradability. However, the chemically cross-linked nanogels usually require complicated procedures or tough conditions. Herein, we report a simple approach to generate chitosan-based nanogels by photo-crosslinking of poor solvent-induced nanoaggregates without requiring any emulsifying agent, catalyst, or external crosslinker. O-nitrobenzyl alcohol-modified carboxymethyl chitosan was synthesized and self-crosslinked into the nanogels in a mixed solution of ethanol and water under 365 nm light irradiation due to UV-induced primary amine and o-nitrobenzyl alcohol cyclization. The nanogels (CMC-NBA NPs) and lactobionic acid-decorated nanogels (LACMC-NBA NPs) displayed a uniform diameter (~200 nm) and excellent stability under physiological conditions. Notably, the nanogels exhibited a high loading content (~28 %) due to π-π stacking and electrostatic interactions between doxorubicin (DOX) and the carriers. These DOX-loaded nanogels showed rapid drug release under slightly acidic conditions. The cell and animal experiments confirmed that LACMC-NBA NPs increased cellular uptake, improved cytotoxicity in tumor cells, and enhanced growth inhibition in vivo than CMC-NBA NPs. Thus, these photo-crosslinked nanogels possess great potential for DOX delivery.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-14
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IF 9.429
Deng Bo,Ma Bing,Ma Yingying,Cao Pei,Leng Xigang,Huang Pengyu,Zhao Yuanyuan,Ji Tianjiao,Lu Xueguang,Liu Lanxia
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 + and CD4 + T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect. Graphical Abstract
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Materials Science & Engineering C-Materials for Biological Applications
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2019
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IF 4.959
Wanling Cai,Mengyu Guo,Xiulan Weng,Wei Zhang,Zuliang Chen
Since Fe 3 O 4 nanoparticles synthesized by plant extracts possess good bio-compatibility and superparamagnetic properties, the possibility of these could be used as a carrier in drug delivery. In this work, doxorubicin hydrochloride (DOX), an anti-cancer drug, loaded on glutaric anhydride-functionalized magnetic nanoparticles (Fe 3 O 4 @SiO 2 -Glu) was investigated at varying pH values for effective drug delivery. Various factors affecting the adsorption of DOX onto the Fe 3 O 4 @SiO 2 -Glu were examined, where the adsorption efficiency of DOX reached 92% at a concentration of 20 mg/L employing 10 mg of Fe 3 O 4 @SiO 2 -Glu at 303 K in pH 7.4. However, the adsorption efficiency of DOX was decreased to 18% at acidic pH value down to 3.0, implicating that the drug releasing process was controlled by pH. Adsorption kinetics was fitting to pseudo-second-order and the isothermal adsorption conformed to Freundlich isotherm. The morphology and surface composition of the synthesized Fe 3 O 4 @SiO 2 -Glu were characterized by SEM, TEM , and N 2 adsorption/desorption isotherms, revealing that the specific surface area being 62.6 m 2 /g and the size ranging from ~30 to 50 nm. The zeta potential results indicated that Fe 3 O 4 @SiO 2 -Glu were negatively charged in various pH from 3 to 8.5. Characterizations by FTIR and UV–Vis techniques suggested that the DOX was absorbed and it can be delivered by Fe 3 O 4 @SiO 2 -Glu.
研究领域:
生物医学工程
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药剂学
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Frontiers in Cell and Developmental Biology
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2021
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IF 6.684
Ye Shiju,Su Lan,Shan Peiren,Ye Bozhi,Wu Shengjie,Liang Guang,Huang Weijian
Background and Purpose: The profibrotic and proinflammatory effects induced by doxorubicin (DOX) are key processes in the development of serious heart damage. Lack of effective drugs and the unclear mechanisms of its side effects limit the clinical treatment of DOX-induced cardiac injury. This study aimed to explore the protective role of LCZ696 and the potential mechanism of Toll-like receptor 2 (TLR2) in doxorubicin-induced cardiac failure.Experimental Approach: DOX (5 mg/kg/week, three times) was used to establish a chronic cardiomyopathy mouse model. Heart function tests, pathology examinations and molecular biology analyses were used to explore the effects of LCZ696 and TLR2 deficiency in vivo and in vitro. Computational docking was applied to predict the key residues for protein-ligand interaction.Key Results: The EF% declined, and the LVIDd, pro-fibrosis marker levels and NF-κB related inflammatory response increased in the chronic cardiomyopathy group induced by DOX. LCZ696 treatment and TLR2 deficiency reversed these heart damage in vivo. In H9C2 cells, pre-treatment with LCZ696 and TLR2 knockdown suppressed the DOX-induced high expression of profibrotic and proinflammatory markers. Moreover, DOX notably increased the TLR2-MyD88 interaction in vivo and in vitro, which was inhibited by LCZ696. Finally, we demonstrated the direct interaction between DOX and TLR2 via hydrogen bonds on Pro-681 and Glu-727 and Pro-681 and Ser-704 may be the key residues by which LCZ696 affects the interaction between DOX and TLR2.Conclusion and Implications: LCZ696 prevents DOX-induced cardiac dilation failure, fibrosis and inflammation by reducing the formation of TLR2-MyD88 complexes. LZC696 may be a potential effective drug to treat DOX-induced heart failure.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2020
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IF 3.232
Guohua Mi,Huanxian Shi,Min Yang,Cunjin Wang,Hong Hao,Jun Fan
Doxorubicin hydrochloride (DOX) is an effective anthracycline anticancer drug . However, the exceeded taken up could induce several side-effects such as cardiotoxicity, alopecia. Therefore, the level of DOX needs to be closely monitored to avoid the occurrence of its side-effects. Herein, we report a novel core CuInSe 2 - shell ZnS quantum dots (CuInSe 2 @ZnS, QDs) and Ag nanoparticles (NPs) fluorescence sensor based on the surface plasmon resonance effect (SPR) of Ag NPs. The CuInSe 2 @ZnS QDs were prepared by water phase reflux method with the 3-mercaptopropionic acid (MPA) as stabilizer and ligand. The fluorescence intensity of CuInSe 2 @ZnS QDs/Ag NPs significantly reduced by DOX, which is mainly based on the electrostatic interaction between the DOX and fluorescence sensors. The inhibition of photoluminescence (ln F 0 /F) was linearly relationship to the concentration of DOX in the range of 2–100 μM with the detection limit as low as 0.05 μM. The as-prepared sensor has a high selectivity and sensitivity to DOX. Furthermore, the new sensor has been successfully applied to the determination of DOX in human serum samples with satisfactory results. Our work provides a clue for developing a novel CuInSe 2 @ZnS QDs/Ag NPs based fluorescence sensor for DOX detection.
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Nanomaterials
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2019
·Vol. 9
·期 2
·188
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IF 4.034
Yu Zhou,Yanming Han,Gaiyun Li,Sheng Yang,Fuquan Xiong,Fuxiang Chu
Due to their exceptional absorption capacity, biodegradability, and non-toxicity, nanoparticles (NPs) from lignin have emerged as vehicles for inorganic particles and drug molecules. However, the method for preparing targeted lignin particles is still complex and lacks sufficient research. Herein, a succinct strategy was proposed for the preparation of targeted lignin-based drug delivery NPs to load Doxorubicin Hydrochloride (DOX). The lignin hollow NPs (LHNPs) were used as a platform for the preparation of targeted delivery material by incorporating magnetic NPs and folic acid (FA) via layer-by-layer self-assembling. The results showed that the surface of LHNPs was covered uniformly by Fe3O4NPs and grafted with folic acid. The folic-magnetic-functionalized lignin hollow NPs (FA-MLHNPs) could respond to magnetic field and folic acid receptors. In addition, the targeting performance of the FA-MLHNPs increased the cellular uptake of NPs in the case of HeLa cells. This research not only supported the modified NPs platform as a highly efficient nano-delivery method but also provided a facile approach to utilize renewable lignin biomaterials.Keywords:lignin;nanoparticles;targeted materials;drug delivery
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2019
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IF 2.705
Qing Shan,Xiaoyu Li,Mei Zheng,Xi Lin,Guotao Lu,Dongming Su,Xiang Lu
Doxorubicin (DOX) is an antitumor drug widely used in hematological tumors and various solid tumors. However, the cardiotoxicity elicited by DOX severely limits its clinical treatment. Dimethyl itaconate (DI), a common form of itaconate, is found many potential targets for prevent heart injury. Here we employed wild type and Nrf2 knockout mice and induced a cardiotoxicity model by administration of DOX to clarify the effects of DI. After treatment with DI, we found that it could effectively alleviate the cardiotoxicity by analyzing morphology, LDH levels and heart weight/body weight ratio changes. Meanwhile we demonstrated that RIP3, a key protein of necrosis, was significantly decreased in DI treated group. Further we observed that treatment with DI could suppress oxidative stress by altering Nrf2/HO-1. Compared with vehicle group, DI could increase the tissue SOD and GSH, and reduce MDA levels, then DHE staining revealed that the level of ROS in DI group reduced by half. Finally, transmission electron microscope (TEM) data showed that treatment with DI obviously decreased the mitochondrial damage. While Nrf2 was ablated in mice, the protective effects of DI were vanished and SOD, GSH, MDA became unchanged related to vehicle group. This report provides the evidence for the protective effects of DI treatment in cardiotoxicity induced by DOX. On mechanisms, DI could reduce the oxidative stress by altering Nrf2/HO-1 pathway and prevent mitochondrial from damage. Taken together, these findings of this paper will afford the new therapeutic targets in DOX related cardiotoxicity.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Li Li,Yang Yang,Yirui Lv,Ping Yin,Ting Lei
Porous CaCO 3 microspheres are nowadays extensively used as a drug delivery system due to their excellent biocompatibility and degradability. However, the stability of vaterite CaCO 3 microspheres is a major problem as a drug carrier. In this work, porous calcite CaCO 3 microspheres are fabricated by calcination of gelatin-CaCO 3 composite microspheres at 550 °C in air. The size and morphology of CaCO 3 microspheres could be well regulated by the addition of gelatin. The structure of the as-prepared porous calcite CaCO 3 microspheres is characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Compared with vaterite CaCO 3 microspheres, porous calcite CaCO 3 microspheres are more stable and exhibit good drug-loading and drug release properties for doxorubicin (DOX), an effective anticancer agent. This study provides an easy and novel approach to prepare stable porous calcite CaCO 3 microspheres, which show promising potential as a carrier for DOX.
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International Journal of Nanomedicine
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2018
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IF 4.37
Yishun Yang,Yuan Zhao,Jinshuai Lan,Yanan Kang,Tong Zhang,Yue Ding,Xinyu Zhang,Lu Lu
Introduction A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. Materials and methods HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. Results DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (−6.7 to −31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 μg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. Conclusion HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.
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BIOCONJUGATE CHEMISTRY
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2015
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IF 4.513
Yushen Jin,Xibo Ma,Shanshan Feng,Xiao Liang,Zhifei Dai,Jie Tian,Xiuli Yue
Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy.
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