COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Shuangni Zhao,Le Van Minh,Na Li,Vasil M. Garamus,Ulrich A. Handge,Jianwen Liu,Rongguang Zhang,Regine Willumeit-Römer,Aihua Zou
The hydrophilic drug Doxorubicin hydrochloride (DOX) paired with oleic acid (OA) was successfully incorporated into nanostructured lipid carriers (NLCs) by a high-pressure homogenization (HPH) method. Drug nanovehicles with proper physico-chemical characteristics (less than 200 nm with narrow size distribution, spherical shape, layered internal organization, and negative electrical charge) were prepared and characterized by dynamic light scattering, zeta potential measurements, transmission electron microscopy, small-angle X-ray scattering and differential scanning calorimetry. The drug loading and entrapment efficiency of DOX-OA/NLCs were 4.09% and 97.80%, respectively. A pH-dependent DOX release from DOX-OA/NLCs, i.e., fast at pH 3.8 and 5.7 and sustained at pH 7.4, was obtained. A cytotoxicity assay showed that DOX-OA/NLCs had comparable cytotoxicity to pure DOX and were favorably taken up by HCT 116 cells. The intracellular distribution of DOX was also studied using a confocal laser scanning microscope. All of these results demonstrated that DOX-OA/NLCs could be a promising drug delivery system with tumor-specific DOX release for cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Hui Xiong,Shi Du,Jiang Ni,Jianping Zhou,Jing Yao
Dual-targeted nanoparticles have been increasingly used to realize greater anti-proliferation effect by attacking double key sites of tumor cells. In order to retain nuclei inhibition effect and enhance DOX-induced apoptosis by mitochondrial pathway simultaneously, hyaluronic acid (HA) modified hydroxyapatite (HAP) nanoparticles (HAP-HA), the functional calcium-based tumor targeting nanoparticles, have been developed. In this nanosystem , HA acts as an active tumor-targeting ligand to bind the CD44 receptors which are overexpressed on the surface of tumor cells while HAP can load and deliver DOX to both nuclei and mitochondria of tumor cells. In this study, DOX-loaded HAP-HA nanoparticles (DOX/HAP-HA) exhibited satisfactory drug loading efficiency which was up to 214.55 ± 51.05 μg mg −1 and showed a uniform nano-scaled particle size. The mitochondrial and nuclei targetability of DOX/HAP-HA was confirmed by confocal laser scanning microscopy analyses. Besides, western blot assay demonstrated that DOX/HAP-HA could markedly enhance mitochondrial cytochrome C leakage and thereby activate apoptotic cascade associated with it. In addition, in vivo anti-tumor efficacy and toxicity evaluation of DOX/HAP-HA indicated that DOX/HAP-HA was more effective and less harmful compared to other groups. DOX/HAP-HA might be a new promising targeted delivery system for effective cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Jing Zhang,Yujie Sun,Baocheng Tian,Keke Li,Lele Wang,Yan Liang,Jingtian Han
In this paper, a CD44-targeted and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) was synthesized by conjugating tumor-shedable hyaluronic acid (HA) on the surface of MSNs via disulfide bonds. Doxorubicin hydrochloride (DOX·HCl) was physically encapsulated into HA modified MSNs (MSNs/SS/HA@DOX) as a model drug. MSNs/SS/HA@DOX (40 nm) had a high drug loading (14.1%) and redox-responsive drug release property. The cellular uptake behaviors of MSNs/SS/HA@DOX by HeLa and LO2 cells were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). MSNs/SS/HA@DOX exhibited higher cellular uptake efficacy via CD44-mediated endocytosis by HeLa cells (CD44 over-expressed cells) than by LO2 cells (CD44 deficient cells). The in vitro cytotoxicity assay demonstrated that MSNs/SS/HA@DOX exhibited higher cytotoxicity to HeLa cells than to LO2 cells. These results indicated that MSNs/SS/HA@DOX might be promising as a multifunctional drug delivery system to improve the anti-tumor efficacy of chemotherapeutic drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 31
·6356-6365
·
IF 4.543
Kaizong Huang,Lingli Zhu,Yunke Wang,Ran Mo,Zichun Hua
Developing a smart cancer drug delivery carrier with enhanced cancer-targeting and effective drug release in tumors is critical for efficient cancer chemotherapy. Herein, we designed a pH-responsive copolymer (PEG-ELP[VH4-70]) that entraps DOX into a hydrophobic core and self-assembles into smart DOX-loaded nanoparticles. The DOX-loaded nanoparticles were stabilized by Zn2+ and disrupted as the pH drops from 7.4 to 5.6. An in vitro study demonstrated that the DOX-loaded nanoparticle system exhibited efficient internalization, triggered the release of DOX into the cytoplasm and enabled the inhibition of tumors effectively. When used to deliver chemotherapeutics to a murine cancer model, PEG-ELP[VH4-70]/DOX accomplished a 4.8-fold suppressed effect relative to the free drug after intravenous injection. This simple strategy can promote preeminent stability for targeting hydrophobic drugs to tumor tissues.
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Xiaohan Zhang,Qiu Li,Xiaodong Sun,Baolei Zhang,Hongxiang Kang,Fuli Zhang,Yiguang Jin
Photodynamic therapy (PDT) is an emerging method for the treatment of cancer. Combination of PDT and chemotherapy is a hot topic though the two therapies could not simultaneously exert their perfect effect in vivo. Here we report a doxorubicin-loaded photosensitizer-core pH-responsive copolymer nanocarrier with high tumor targeting and anticancer effects due to integration of PDT with chemotherapy. The pH-responsive photosensitizer-core four-armed star-shaped copolymer, [methoxy-poly(ethylene glycol)-poly(2-(N,N-diethylamino)ethyl methacrylate)-poly(ε-caprolactone)]4-zinc β-tetra-(4-carboxyl benzyloxyl)phthalocyanine (PDCZP), was prepared, which was a molecular spherical nanocarrier in aqueous media. The carriers changed from small at high pH to large at low pH (51, 105, and 342 nm at pH 7.4, 6.5, and 5.0, respectively) and the zeta potential gradually increased (7.15, 16.2, and 26.1 mV at the above pH, respectively). PDCZP had a longer emission wavelength (max. 677 nm) than the parent photosensitizer, favoring light penetration through biological tissues. The singlet oxygen (1O2) quantum yield of PDCZP was 0.41. Doxorubicin (DOX) showed rapid release from PDCZP in the acidic media. More importantly, the drug-loaded nanocarriers showed the better in vitro and in vivo anticancer effects under lighting on MCF-7, SW480 cells and HepG2 cells and the murine hepatocellular carcinoma H22 models than the other groups. PDCZP showed a high tumor targeting effect based on the enhanced permeation and retention effect and its small size. The photosensitizer-core nanocarrier is a promising photodynamic nanocarrier for integrating other therapies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2016
·Vol. 8
·期 9
·5089-5097
·
IF 7.76
Abdul Hakeem,Fouzia Zahid,Ruixue Duan,Muhammad Asif,Tianchi Zhang,Zhenyu Zhang,Yong Cheng,Xiaoding Lou,Fan Xia
Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2017
·
IF 0
Tianmu Hu,Anwar Saeed Ahmed Qahtan,Lei Lei,Zhixin Lei,Dapeng Zhao,Hemin Nie
In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.
✓ 已验证
产品关联
DOI
PubMed
Nanoscale
·
2016
·Vol. 8
·期 43
·18400-18411
·
IF 7.76
Sen Lin,Tong Li,Peiling Xie,Qing Li,Bailiang Wang,Lei Wang,Lingli Li,Yuqin Wang,Hao Chen,Kaihui Nan
Targeted delivery of cytotoxic drugs to tumour tissue has great importance for successful chemotherapy. Legumain is an asparaginyl endopeptidase that is highly up-regulated in a number of solid tumours. The aim of this work was to prepare a novel hyaluronic acid (HA) based legumain sensitive nanogel for the delivery of doxorubicin with a high targeting efficiency both in vitro and in vivo. The legumain sensitive property is achieved by the conjugation of doxorubicin with HA via a legumain substrate peptide bridge. This HA derivative is further crosslinked in a water/oil solvent system to form a polygonal nanogel. Doxorubicin released in the tumour tissue is sustained thanks to the combined action of legumain and hyaluronidase, which are both overexpressed in tumour tissues. Hyaluronic acid could act as a targeting agent to CD44 (HA receptor), which further improved the in vivo target effect and enhanced in vitro cellular uptake. The developed nanogel exhibited a high therapeutic index that improved tumour inhibition effects and reduced system toxicity in a lung cancer mice model. These results highlighted the advantages of using this multi-functional material for a successful delivery of doxorubicin against cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Jing Yang,Yanping Wu,Yan Shen,Changren Zhou,Yi-Fang Li,Rong-Rong He,Mingxian Liu
Halloysite nanotubes (HNTs) are natural aluminosilicates with unique hollow lumen structure, also having high specific area, good biocompatibility, nontoxicity, and low price. Here, we designed a chitosan oligosaccharide-grafted HNTs (HNTs-g-COS) as a doxorubicin (DOX) carrier for treating breast cancer both in vitro and in vivo. The structure of HNTs-g-COS was first characterized by various methods. HNTs-g-COS showed positively charged surface and improved hemocompatibility. DOX-loaded HNTs-g-COS (DOX@HNTs-g-COS) released in cell lysate in a controlled manner. The IC50 value of DOX@HNTs-g-COS toward MCF-7 cells was 1.17 μg mL–1, while it was 2.43 μg mL–1 for free DOX. DOX@HNTs-g-COS increased the apoptosis effects of MCF-7 cells as shown in flow cytometry results. Also, reactive oxygen species of cells induced by DOX@HNTs-g-COS were drug-dose-dependent. DOX@HNTs-g-COS could enter the MCF-7 cells and induce mitochondrial damage as well as attack the nuclei. The in vivo antitumor effect of DOX@HNTs-g-COS was investigated in 4T1-bearing mice. The tumor-inhibition ratio of DOX@HNTs-g-COS was 83.5%, while it was 46.1% for free DOX. All mice treated with DOX@HNTs-g-COS survived over 60 days. DOX@HNTs-g-COS showed fewer ruptured cardiomyocytes and no obvious systemic toxicity. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed promising applications in tumor treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science and Engineering B-Advanced Functional Solid-State Materials
·
2017
·
IF 2.552
Zhifeng Xu,Peihong Deng,Junhua Li,Li Xu,Siping Tang
In this work, a new type of fluorescent probe for detection of doxorubicin has been constructed by the combined use of fluorescence resonance energy transfer (FRET) technology and molecular imprinting technique (MIT). Using doxorubicin as the template, the molecularly imprinted polymer thin layer was fabricated on the surfaces of carbon dot (CD) modified silica by sol-gel polymerization. The excitation energy of the fluorescent donor (CDs) could be transferred to the fluorescent acceptor (doxorubicin). The FRET based fluorescent probe demonstrated high sensitivity and selectivity for doxorubicin. The detection limit was 13.8 nM. The fluorescent probe was successfully applied for detecting doxorubicin in doxorubicin-spiked plasmas with a recovery of 96.8–103.8%, a relative standard deviation (RSD) of 1.3–2.8%. The strategy for construction of FRET-based molecularly imprinted materials developed in this work is very promising for analytical applications.
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Jaili Li,Ting Luo,Yao Zhao,Dou Wang,Yuanxiang Jin,Zufang Wu,Guiling Yang,Xingjiang Qi
Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Haiqiu Wu,Haojie Jin,Cun Wang,Zihao Zhang,Haoyu Ruan,Luyan Sun,Chen Yang,Yongjing Li,Wenxin Qin,Changchun Wang
Combination chemotherapy has been proposed to achieve synergistic effect and minimize drug dose for cancer treatment in clinic application. In this article, the stimuli-responsive polymeric nanogels (<100 nm in size) based on poly(acrylic acid) were designed as codelivery system for doxorubicin and cisplatin to overcome drug resistance. By chelation, electrostatic interaction, and π–π stacking interactions, the nanogels could encapsulate doxorubicin and cisplatin with designed ratio and high capacity. Compared with free drugs, the nanogels could deliver more drugs into MCF-7/ADR cells. Significant accumulation in tumor tissues was observed in the biodistribution experiments. The in vitro antitumor studies demonstrated the superior cell-killing activity of the nanogel drug delivery system with a combination index of 0.84, which indicated the great synergistic effect. All the antitumor experimental data revealed that the combination therapy was effective for the multidrug-resistant MCF-7/ADR tumor with reduced side effects.
✓ 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）