COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Si Sun,Nihad Cheraga,Han-Ning Jiang,Qian-Ru Xiao,Peng-Cheng Gao,Yang Wang,Ying-Ying Wei,Xiao-Wei Wang,Yong Jiang
A variety of three-dimensional DNA assemblies have been proposed as drug carriers owing to their good biocompatibility and easy fabrication. In this study, inspired by the structure of cockleburs, a novel aptamer-tethered DNA assembly was developed for effective targeted drug delivery. The Apt-nanocockleburs were fabricated via a facile process of DNA base pairing: four complementary DNA single strands, including one aptamer-ended strand and three sticky-end strands, were applied to pair with each other. The main body of the nanocockleburs can load doxorubicin (Dox) whilst the covered aptamer spines bind to the target MCF-7 cells. The self-assembled Apt-nanocockleburs exhibit higher cell uptake as well as increased cytotoxicity to MCF-7 cells than DNA nanocockleburs without aptamers. This study provided a DNA constructing platform to produce new drug carriers with high selectivity for cancer targeted drug delivery.
研究领域:
纳米技术
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药学
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生物医学工程
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 16
·e70032
·
IF 4.3
Qinbing Xue,Bing Wang,Jie Feng,Chaoyu Li,Miao Yu,Yan Zhao,Zheng Qi
Breast cancer (BC) is one of the most common types of cancer among women worldwide. Lycorine ( Lycoris radiata ), a small molecule derived from the traditional Chinese herb Amaryllidaceae plants, has appeared potential effect on inhibiting the growth of cancer cells and inducing apoptosis in various types of cancer with minor side effects. To discuss the therapeutic effects and molecular mechanisms of lycorine on BC established by lycorine-treated S180 tumour-bearing mice in vivo. Furthermore, both the mitotic and microtubule assembly dynamics genes were performed by qPCR assays, and the protein expression associated with mitotic arrest was investigated by western blot. Lycorine was demonstrated to reduce sarcoma growth of S180 tumour-bearing mice and inhibit the proliferation of MCF-7 cells in concentration-dependent manner. Moreover, lycorine induced M phase cell cycle arrest via interfering with the mitotic apparatus regulated the expression of 20 genes and 15 proteins in cell cycle progression. Furthermore, this study confirmed that the potential effect of lycorine on BC might be mediated by cell cycle arrest in M phase for the first time. These results would be the consequence of exploitation of lycorine as a potential drug for BC therapy, however further preclinical and clinical studies are still needed.
研究领域:
肿瘤学
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药理学
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Qin-Qin Gao,Chuan-Min Zhang,En-Xia Zhang,Hui-Ying Chen,Yu-Hong Zhen,Shu-Biao Zhang,Shu-Fen Zhang
As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.
研究领域:
药剂学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Yue Yang,Xiaoyu Lu,Qi Liu,Yu Dai,Xiaojie Zhu,Yanli Wen,Jiaqiu Xu,Yang Lu,Di Zhao,Xijing Chen,Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies. The liposomes (weight ratio of DOX to PA = 1:20, DOX 1 /PA 20 -LPs) exhibited the strongest synergistic effects, combination index was 0.38, 0.56, and 0.05 in MCF-7, HepG2, and A549 cells, respectively. In vitro cellular uptake study, the intercellular concentration of DOX in DOX 1 /PA 20 -LPs was 2.5-fold greater than DOX loaded liposome, and DOX 1 /PA 20 -LPs was taken in not only by macropinocytosis, but also by clathrin-mediated endocytosis. Intracellular distribution experiment showed that DOX 1 /PA 20 -LPs efficiently concentrated in the nucleus. In vivo studies indicated that co-encapsulated liposome not only showed the strongest antitumor ability by tumor growth suppression, but also significantly enhanced the safety by the change of body weight and reduced damages to other tissues (evidenced by histopathology study). These results indicated that DOX and PA co-delivery liposome successfully enhanced the anticancer efficacy and mitigated the toxicities of DOX, which displayed potential for clinical application with enhanced safety and efficacy.
研究领域:
药理学
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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
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2014
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IF 2.305
Guang-Gang Gao,Guo-Biao Xu,Jin-Lian Li,Ji-Wen Cui,Dong-Mei Wu,Hong-Bin Qiu
Using an ultrasensitive chemically reduced graphene oxide and ionic liquid modified glass carbon electrode (RGI–GCE), separated electrochemical signals of adenine and hypoxanthine in both human breast cancer (MCF-7) and mouse embryonic fibroblast (BALB/3T3) cells were observed. For the first time, low-level expression of purine bases in noncancerous BALB/3T3 cells can be electrochemically monitored. The metabolism of purine bases in carcinogen agent-contaminated BALB/3T3 cells was also investigated through the change of electrochemical signals ascribed to different purine bases, which opens a new electrochemical approach to the exploration of a low-level purine mechanism in noncancerous cells.
研究领域:
生物化学
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医学检测
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材料科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 27
·20890-20899
·
IF 3.84
Minghui Xu,Junmin Qian,Aili Suo,Weijun Xu,Rongrong Liu,Hongjie Wang
Combination of chemotherapy and small interfering RNA (siRNA)-based therapy has emerged as a promising approach for cancer treatment with the synergistic effect. In this study, a novel terpolymer methoxy poly(ethylene glycol)-block-poly(N,N-dimethylaminopropyl methacrylamide)-block-poly(acrylhydrazine) (mPEG-b-PDMAPMA-b-PAH) with a disulfide linkage between mPEG and PDMAPMA blocks was developed for the intracellular targeted co-delivery of adriamycin and P-gp siRNA. The terpolymer was synthesized by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization of N,N-dimethylaminopropyl methacrylamide and N-tert-butoxycarbonyl-N′-acryl hydrazine (Boc-acrylhydrazine) in the presence of a PEGylated macro-RAFT agent, followed by Boc-deprotection. The terpolymer could chemically conjugate adriamycin via an acid-cleavable hydrazone bond and simultaneously condense the negatively charged siRNA through electrostatic interactions at an N/P ratio of 2. The resultant adriamycin-conjugated nanoparticles/siRNA complexes (ADR-NPs/siRNA complexes) showed a spherical morphology and had an average diameter of 186 nm. The release profiles of the two payloads from the ADR-NPs/siRNA complexes exhibited a pH/reduction dual-dependent sustained release behavior. The ADR-NPs/siRNA complexes could simultaneously deliver adriamycin and siRNA efficiently into MCF-7/ADR cells and significantly inhibit their growth in a synergistic fashion. All the results indicated that the terpolymer mPEG-b-PDMAPMA-b-PAH could serve as a potential vehicle for the combination of chemotherapy and gene therapy.
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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聚合物化学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2019
·
IF 3.31
Yun Li,Yueqin Li,Nana Wang,Dong Lin,Xiaohui Liu,Yong Yang,Qinwei Gao
Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙− radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙−superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma
研究领域:
无机化学
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生物化学
·
药理学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Yufan Guo,Xiuru Yang,Yihong Zhang,Fazhen Luo,Juan Yang,Xupeng Zhang,Jinxia Mi,Yan Xie
Cancer multidrug resistance (MDR) dramatically hindered the efficiency of standard chemotherapy. Mitochondria are highly involved in the occurrence and development of MDR; thus, inducing its malfunction will be an appealing strategy to treat MDR tumors. In this paper, a natural polysaccharides-based nanoplatform (TDTD@UA/HA micelles) with cell and mitochondria dual-targeting ability was facilely fabricated to co-deliver ursolic acid (UA) and doxorubicin (DOX) for combinatorial MDR therapy. TDTD@UA/HA micelles featured a spherical morphology, narrow size distribution (∼140 nm), as well as favorable drug co-loading capacity (DOX: 8.41 %, UA : 9.06 %). After hyaluronic acid (HA)-mediated endocytosis , the lysosomal hyaluronidase promoted the degradation of HA layer and then the positive triphenylphosphine groups were exposed, which significantly enhanced the mitochondria-accumulation of nano micelles . Subsequently, DOX and UA were specifically released into mitochondria under the trigger of endogenous reactive oxygen species (ROS), followed by severe mitochondrial destruction through generating ROS, exhausting mitochondrial membrane potential, and blocking energy supply, etc. ; ultimately contributing to the susceptibility restoration of MCF-7/ADR cells to chemotherapeutic agents. Importantly, TDTD@UA/HA micelles performed potent anticancer efficacy without distinct toxicity on the MDR tumor-bearing nude mice model. Overall, the versatile nanomedicine represented a new therapeutic paradigm and held great promise in overcoming MDR-related cancer.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Tingting Meng,Binbin Lu,Shihong Shao,Ming Yuan,Xuan Liu,Hong Yuan,Xuan Huang,Fuqiang Hu
P-glycoprotein (P-gp) is a major efflux transporter overexpressed on multidrug resistant tumor cells and responsible for pumping drugs out. If anti-tumor drugs are given when P-gp level is low, satisfactory treatment efficiency may be achieved. Thus, a P-gp down-regulating siRNA (siMDR1) and doxorubicin (DOX) were applied to eliminate multidrug resistant breast cancer cells (MCF-7/ADR). A redox-responsive glucolipid conjugate (CSO-ss-SA) was used to condense siRNA (CSO-ss-SA/siRNA) and encapsulate DOX (CSO-ss-SA/DOX) separately. They responded to the high reducing environment of tumor cells and fast released the payload. CSO-ss-SA/siMDR1 silenced MDR1 gene and resulted in a transient decrease of P-gp. Sequentially, DOX formulation (CSO-ss-SA/DOX or DOX·HCl) was delivered when P-gp was reduced to the lowest level. After pretreatment by CSO-ss-SA/siMDR1, cytotoxicity of CSO-ss-SA/DOX and DOX·HCl against MCF-7/ADR cells were 6.4 or 3.4-fold respectively of that treated by DOX·HCl alone, which exhibited increased cytotoxin sensitivity of drug resistant cells and maximized therapeutic outcomes. These results revealed that the sequential treatment strategy of CSO-ss-SA/siRNA and CSO-ss-SA/DOX hold potential in achieving an optimal overcoming multidrug resistance efficiency.
研究领域:
药学
·
纳米技术
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Yun Wang,Feihu Wang,Ying Liu,Shaohui Xu,Yuanyuan Shen,Nianping Feng,Shengrong Guo
Effects of nanosized drug delivery systems on cancer are often compromised due to their low drug loadings, premature drug release and multi-drug resistance (MDR). Herein, we reported a glutathione detonated and pH responsive nano-cluster of Au nanorods (AuNRs) with chemotherapeutic doxorubicin (DOX) and pre-chemosensitizer polycurcumin to treat MCF-7/ADR cells. The nano-cluster was prepared by self-assembling of AuNRs conjugated with DOX and amphiphilic poly(curcumin-co-dithiodipropionic acid)-b-biotinylated poly(ethylene glycol) via an emulsion/solvent evaporation technique, termed AuNR Cluster. The AuNR Cluster had a high drug loading (31.5% DOX), presenting much better aqueous solubility and stability at physiological pH than their individual AuNRs. The AuNR Cluster could be detonated to be their individual AuNRs at an intracellular concentration level of glutathione (GSH) (5 mM) and triggered to release DOX at an acidic pH (pH 6.8 or 5.0), which effectively facilitated cellular uptake of DOX (607 vs 356 a.u. for AuNRs at 12 h) and inhibited DOX efflux (471.33 vs 39.17 a.u. for free DOX at 24 h). The IC 50 value of DOX against MCF-7/ADR cells for AuNR Cluster was 4.15 µg/mL, much lower than that for free DOX (90.97 µg/mL). The AuNR Cluster took much more photothermal effects than their corresponding AuNRs and presented enhanced anti-tumor effect (IC 50 : 2.61 µg/mL) under 808 nm laser irradiation. Statement of Significance Nano-sized drug delivery systems for anti-MDR cancer is still a challenging task. Herein, AuNR Cluster was self-assembled by individual AuNRs via emulsion/solvent evaporation technique, having a structure consisting of hydrophobic DOX/PCDA-AuNR core and hydrophilic biotin-PEG chain shell. AuNR Cluster is detonated to disintegrate and yield its individual AuNRs at an intracellular concentration level of glutathione (5 mM) and triggered to release DOX at an acidic pH (6.8 or 5.0). In comparison with its individual AuNRs, AuNR Cluster has better water solubility and stability, greater photothermal effects under NIR irradiation, bigger cytotoxicity against MCF-7/ADR cells. AuNR Cluster is expected to be a potential nanomedicine for treatment of MDR cancer.
研究领域:
纳米医学
·
癌症研究
·
药物递送系统
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Chunlai Feng,Haisheng Zhang,Jiaming Chen,Siqi Wang,Yuanrong Xin,Yang Qu,Qi Zhang,Wei Ji,Fumiyoshi Yamashita,Mengjie Rui,Ximing Xu
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro , combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained co-loaded lipodisks were approximately 30 nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro , as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo , potentially enhancing the clinical outcome of synergistic therapy.
研究领域:
癌症治疗
·
药学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Jianwen Zhao,Fengfeng Zhao,Xiyong Wang,Xiaobo Fan,Guoqiu Wu
A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide-fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）