COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2019
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IF 3.131
Ying Wang,Jingwen Chen,Qianqian Han,Qiang Luo,Hongmei Zhang,Yanqing Wang
Lentinan(LNT) has many kinds of pharmacological activities such as antioxidative activities, hypoglycemic effect, anti-hyperlipidemic effect and so on. Here, LNT was used as the skeleton material to couple with doxorubicin(DOX) by forming the LNT–DOX conjugates in order to enhance anticancer effects and reduce the systemic side effects of DOX. Based on the screening results, we observed that LNT can acted as an antitumor carrier for release of DOX with pH-responsive. DOX release from conjugates was 63.1% at pH 5.0 for up to 48 h, whereas 13.6% of DOX release was observed at pH 7.4 in phosphate buffered saline . The grafting rate of LNT-DOX conjugates was 6.5±0.65 mg/100 mg DOX content. The morphology results showed that LNT-DOX conjugates were considerably more amorphous than LNT. LNT linked by DOX basically maintained the original structure and rheology in water solution. The in vitro anticancer activity of LNT–DOX conjugates was higher than that of free DOX. It is important that LNT–DOX conjugates can enhance anticancer effects in breast cancer cells and decrease the cytotoxocity effects against human normal cells. This work proved that the LNT–DOX conjugates might be suitable for building anticancer drug platform in the course of chemotherapy.
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高影响因子
APPLIED SURFACE SCIENCE
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2017
·
IF 3.387
Shasha Hong,Zengbo Li,Chenzhong Li,Chuan Dong,Shaomin Shuang
The Fe 3 O 4 @PPy-HA-β-CD nanocomposites as the novel nanocarrier were prepared by grafting ethylenediamine derivative of β-CD to the surface of polypyrrole-coated magnetic nanoparticles (Fe 3 O 4 @PPy) via using hyaluronan (HA) as the intermediate linker. HA was also the efficient target ligand for CD44. The as-prepared drug carrier was characterized by TEM, TGA, XRD, and VSM and used for the delivery of doxorubicin hydrochloride (DOX) with the high loading content of 447 mg/g. The multilayer Freundlich isotherm model was found to be a good fit for the loading of the drug carrier for DOX. Significant NIR-triggered release of DOX was observed in a weak acidic pH. And the release data in vitro was well described using the Retiger-Pepper kinetic model. Furthermore, MTT assay and confocal microscopy against Hep-G2 cells clearly illustrated that the drug carrier had no associated cytotoxicity and could easily enter the cells. The release and accumulation of DOX were observed in the cell nuclei. Thus, the DOX-loaded drug carrier killed the cancer cells efficaciously and minimized adverse side effects due to its target effect. These results suggested the as-prepared drug carrier would be of great potential for the controlled release and targeted delivery of DOX.
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MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 2
·1-8
·
IF 5.3
Ou Dan,Yan Huixian,Chen Zuanguang
Based on the electrochemical impedance method, a marker-free biosensor with aptamer as a biometric element was developed for the determination of doxorubicin (DOX). By combining aptamer with rigid tetrahedral DNA nanostructures (TDNs) and fixing them on the surface of gold electrode (GE) as biometric elements, the density and directivity of surface nanoprobes improved, and DOX was captured with high sensitivity and specificity. DOX was captured by immobilized aptamers on the GE, which inhibited electron transfer between the GE and [Fe(CN)6] 3− / 4− in solution, resulting in a change in electrochemical impedance. When the DOX concentration was between 10.0 and 100.0 nM, the aptasensor showed a linear relationship with charge transfer resistance, the relative standard deviation (RSD) ranged from 3.6 to 5.9%, and the detection limit (LOD) was 3.0 nM. This technique offered a successful performance for the determination of the target analyte in serum samples with recovery in the range 97.0 to 99.6% and RSD ranged from 4.8 to 6.5%. This method displayed the advantages of fast response speed, good selectivity, and simple sensor structure and showed potential application in therapeutic drug monitoring. Graphical Abstract
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高影响因子
BIOELECTROCHEMISTRY
·
2024
·
IF 4.8
Yunzhi Zhao,Ying Hao,Min Cui,Na Li,Bao Sun,Yu Wang,Haiyan Zhao,Cong Zhang
Doxorubicin (DOX) is a clinical chemotherapeutic drug and patients usually suffer from dose-dependent cytotoxic and side effects during chemotherapy process with DOX. Therefore, developing a reliable strategy for DOX analysis in biological samples for dosage guidance during chemotherapy process is of great significance. Herein, a sensitive and selective electrochemical biosensor for DOX detection was designed based on gold nanoparticles (AuNPs) and DNA tetrahedron (TDN) nanoprobe bifunctional glassy carbon electrode that could detect DOX in human serum and cell lysate samples. AuNPs not only could enhance electron transfer efficiency and detection sensitivity, but also could improve the biocompatibility of electrode. TDN nanoprobes were employed as specific DOX bind sites that could bind abundant DOX through intercalative characteristics to contribute to sensitive and selective detection. Under the optimal conditions, the proposed TDN nanoprobes-based DOX biosensor exhibited a wide linear range that ranged from 1.0 nM to 50 μM and a low detection limit that was 0.3 nM. Moreover, the proposed DOX biosensor displayed nice selectivity, reproducibility and stability, and was successfully applied for DOX detection in human serum and cell lysate samples. These promising results maybe pave a way for DOX dosage guidance and therapeutic efficacy optimization in clinic.
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高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Huicong Zhou,Huanjiao Sun,Shixian Lv,Dawei Zhang,Xuefei Zhang,Zhaohui Tang,Xuesi Chen
Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue. Briefly, doxorubicin (DOX) was conjugated to carboxyl-terminated 4-arm poly(ethylene glycol) through a tetrapeptide linker, alanine-alanine-asparagine-leucine (AANL), which was one of the substrates of legumain , an asparaginyl endopeptidase that was found presented in plants, mammals and also highly expressed in human tumor tissues. Hereinafter, the polymer-DOX conjugate was termed as 4-arm PEG-AANL-DOX. Dynamic laser scattering (DLS) and transmission electron microscopy (TEM) measurements indicated that the 4-arm PEG-AANL-DOX could self-assemble into micelles in aqueous solution. Drug release and in vitro cytotoxicity studies revealed that the 4-arm PEG-AANL-DOX could be cleaved by legumain. Ex vivo DOX fluorescence imaging measurements demonstrated that the 4-arm PEG-AANL-DOX had an improved tumor-targeting delivery as compared with the free DOX·HCl. In vivo studies on nude mice bearing MDA-MB-435 tumors revealed that the 4-arm PEG-AANL-DOX had a comparable anticancer efficacy with the free DOX·HCl but without DOX-related toxicities to normal tissues as measured by body weight change and histological assessments, indicating that the 4-arm PEG-AANL-DOX had an improved therapeutic index for cancer therapy. Statement of Significance Herein we describe the construction of a novel tumor environment-sensitive delivery system through the instruction of a legumain-cleavable linkage to a polymer-DOX conjugate (4-arm PEG-AANL-DOX). This particular design strategy allows for polymer-DOX conjugates to be delivered in a tumor-specific manner and selectively activable in tumor microenvironment so that it can combine the advantages of tumor-specific delivery and tumor intracellular microenvironment-triggered release systems.
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Theranostics
·
2016
·
IF 8.854
Tangjian Cheng,Jinjian Liu,Jie Ren,Fan Huang,Hanlin Ou,Yuxun Ding,Yumin Zhang,Rujiang Ma,Yingli An,Jianfeng Liu,Linqi Shi
Chemotherapy for cancer treatment has been demonstrated to cause some side effects on healthy tissues and multidrug resistance of the tumor cells, which greatly limits therapeutic efficacy. To address these limitations and achieve better therapeutic efficacy, combination therapy based on nanoparticle platforms provides a promising approach through delivering different agents simultaneously to the same destination with synergistic effect. In this study, a novel green tea catechin-based polyion complex (PIC) micelle loaded with doxorubicin (DOX) and (-)-Epigallocatechin-3-O-gallate (EGCG) was constructed through electrostatic interaction and phenylboronic acid-catechol interaction between poly(ethylene glycol)- block -poly(lysine- co -lysine-phenylboronic acid) (PEG-PLys/PBA) and EGCG. DOX was co-loaded in the PIC micelles through π-π stacking interaction with EGCG. The phenylboronic acid-catechol interaction endowed the PIC micelles with high stability under physiological condition. Moreover, acid cleavability of phenylboronic acid-catechol interaction in the micelle core has significant benefits for delivering EGCG and DOX to same destination with synergistic effects. In addition, benefiting from the oxygen free radicals scavenging activity of EGCG, combination therapy with EGCG and DOX in the micelle core could protect the cardiomyocytes from DOX-mediated cardiotoxicity according to the histopathologic analysis of hearts. Attributed to modulation of EGCG on P-glycoprotein (P-gp) activity, this kind of PIC micelles could effectively reverse multidrug resistance of cancer cells. These results suggested that EGCG based PIC micelles could effectively overcome DOX induced cardiotoxicity and multidrug resistance.
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高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2016
·Vol. 21
·期 4
·685-696
·
IF 4.938
Pengzhou Hang,Jing Zhao,Li Sun,Minghui Li,Yu Han,Zhimin Du,Yue Li
The clinical application of doxorubicin (Dox) is limited by its adverse effect of cardiotoxicity. Previous studies have suggested the cardioprotective effect of brain-derived neurotrophic factor (BDNF). We hypothesize that BDNF could protect against Dox-induced cardiotoxicity. Sprague Dawley rats were injected with Dox (2.5 mg/kg, 3 times/week, i.p.), in the presence or absence of recombinant BDNF (0.4 μg/kg, i.v.) for 2 weeks. H9c2 cells were treated with Dox (1 μM) and/or BDNF (400 ng/ml) for 24 hrs. Functional roles of BDNF against Dox-induced cardiac injury were examined both in vivo and in vitro . Protein level of BDNF was reduced in Dox-treated rat ventricles, whereas BDNF and its receptor tropomyosin-related kinase B (TrkB) were markedly up-regulated after BDNF administration. Brain-derived neurotrophic factor significantly inhibited Dox-induced cardiomyocyte apoptosis, oxidative stress and cardiac dysfunction in rats. Meanwhile, BDNF increased cell viability, inhibited apoptosis and DNA damage of Dox-treated H9c2 cells. Investigations of the underlying mechanisms revealed that BDNF activated Akt and preserved phosphorylation of mammalian target of rapamycin and Bad without affecting p38 mitogen-activated protein kinase and extracellular regulated protein kinase pathways. Furthermore, the beneficial effect of BDNF was abolished by BDNF scavenger TrkB-Fc or Akt inhibitor. In conclusion, our findings reveal a potent protective role of BDNF against Dox-induced cardiotoxicity by activating Akt signalling, which may facilitate the safe use of Dox in cancer treatment.
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ACS Sustainable Chemistry & Engineering
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2017
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IF 5.951
Doudou Hu,Zongpu Xu,Zeyun Hu,Binhui Hu,Mingying Yang,Liangjun Zhu
Silk-based nanoparticles have been exhibiting an increasing potential for use as drug delivery systems due to their great versatility. To extend applications of silk sericin in nanomedicine and improve the performance of silk-based nanoparticles in drug delivery, a facile two-step cross-linking is attempted, for the first time, to fabricate surface charge-reversal silk sericin-based nanoparticles (SSC@NPs) by introducing chitosan into silk sericin. The results suggest stable SSC@NPs are formed with a negative surface charge in a neutral environment. Under mildly acidic conditions, however, surface charge of SSC@NPs undergoes a negative-to-positive conversion. It proves that pH can regulate surface charge of SSC@NPs. It is the increased amino/carboxyl ratio in SSC@NPs that explains the underlying mechanism of the charge conversion property of SSC@NPs. Furthermore, the positively charged SSC@NPs triggered by tumor acidic microenvironment (pH 6.0) result in a 6.0-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. In addition, an anticancer drug doxorubicin (DOX) is readily loaded into SSC@NPs and released in a pH-dependent manner. This work provides a simple method to fabricate smart pH-responsive nanoparticles for anticancer drug delivery.
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高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Lu Han,Cui Tang,Chunhua Yin
The application of cytotoxic chemotherapeutics in cancer therapy has been largely restricted by their lack of selectivity. Despite the existence of numerous targeted delivery systems, it is practically challenging to develop one single system to simultaneously cover tumor-targeted delivery of chemotherapeutics at the tissue, cellular, and subcellular levels. To solve this problem, pH-responsive core–shell structured nanoparticles (CSNPs) were self-assembled in this study to provide triple-stage targeted delivery of doxorubicin (DOX) from the injection site to the nuclei of cancer cells. Amino-functionalized mesoporous silica nanoparticles (MSN) were doubly modified with TAT peptide and acid-cleavable polyethylene glycol (PEG) as the DOX-loaded cationic core. The anionic shell was constituted by galactose-modified poly(allylamine hydrochloride)-citraconic anhydride, a hepato-carcinoma-targeting polymer with charge-reversible property. In vitro results showed that PEG effectively reduced protein adsorption and phagocytic capture of CSNPs in the circulating blood (pH 7.4), thus facilitating passive accumulation in tumors (tissue level). Following PEG detachment via acidic hydrolysis in tumor microenvironment (pH 6.5), the exposed galactose ligands endowed CSNPs with active internalization into hepato-carcinoma cells (cellular level). Afterward, the acidity in endosomes and lysosomes (pH 5.0) triggered the conversion of anionic shell into positive charges, leading to core–shell disassembly and subsequent TAT-mediated delivery of DOX to the nuclei (subcellular level). Importantly, the efficiencies of each targeting moiety were nicely preserved when combining together in CSNPs. As a result, improved tumorous distribution and potent therapeutic efficacy of CSNPs were noted in tumor-bearing mice at a relatively low dose. CSNPs therefore provide an efficient and nontoxic platform for the targeted delivery of antitumor drugs.
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Materials Science & Engineering C-Materials for Biological Applications
·
2015
·
IF 3.088
Shuang Xu,Yan Li,Zhenjie Chen,Cuilan Hou,Tong Chen,Zhigang Xu,Xiaoyu Zhang,Haixia Zhang
Mesoporous silica nanoparticles (MSNs) combining gold particles (MSNs–Au) were synthesized as nanocarriers for glutathione (GSH) and pH dual-sensitive intracellular controlled release of the anti-cancer drug doxorubicin (DOX). The MSNs were used as an adsorbent for DOX, and the ultra-small gold nanospheres (Au NPs) partly operated as gatekeepers to control the release of DOX from the pores of MSNs and as the driver of drug release in the presence of GSH due to the association between GSH and Au particles. Under different pH conditions, DOX release changed due to different levels of dissociation between the –SH group on the MSNs and the Au particles. The composition, morphology, and properties of the as-prepared composites were characterized by elemental analysis, fluorescence spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, nitrogen adsorption–desorption, thermal gravimetric and UV–visible spectroscopy. The in vitro release experiments showed that these smart nanocarriers effectively avoided drug leakage in the neutral media. Cytotoxicity and imaging studies also indicated that DOX-loaded Au-MSNs ( [email protected] –Au) had a significant inhibitory effect on the growth of Tca8113 cells and sustained the release rate of DOX
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高影响因子
APPLIED SURFACE SCIENCE
·
2014
·
IF 2.538
Juan Wu,Yujiao Wang,Wei Jiang,Shanshan Xu,Renbing Tian
This study focuses on the synthesis and characterization of recyclable clusters of magnetic nanoparticles (CMNPs) as doxorubicin carriers for cancer therapy. Fe 3 O 4 nanoparticles were used as magnetically responsive carriers, the modified polyethylene glycol dicarboxylic acid (APS-PEG-TFEE) acted as a steady bridge between Fe 3 O 4 and drug. The prepared CMNPs exhibited a size within 20 nm, good stability and super-paramagnetic responsibility ( M s 62.02 emu/g); doxorubicin (DOX) can be successfully loaded to CMNPs at a loading rate of 76.19% by electrostatic interaction. Moreover, the release studies in vitro showed that the drug-loaded carriers (CMNPs-DOX) had excellent pH-sensitivity, 76.16% of DOX was released within 72 h at pH 4.0, and the secondary drug loading rate was nearly 52%. WST-1 assays in model breast cancer cells (MCF-7) demonstrated that CMNPs-DOX exhibited high anti-tumor activity, while the CMNPs were practically non-toxic. Thus, our results revealed that CMNPs would be a competitive candidate for drug delivery carriers and CMNPs-DOX could be used in targeted cancer therapy in the near future.
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JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2014
·Vol. 52
·期 13
·1771-1780
·
IF 3.245
Yanfeng Chu,Huan Yu,Yingying Ma,Yunti Zhang,Weihai Chen,Guangyan Zhang,Hua Wei,Xianzheng Zhang,Renxi Zhuo,Xulin Jiang
Novel pH and reduction dual-sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy-poly(ethylene glycol)- b -poly[(benzyl- l -aspartate)- co -( N -(3-aminopropyl) imidazole- l -aspartamide)] [ m PEG-SS-P(BLA- co -APILA), MPBA] synthesized by a combination of ring-opening polymerization and side-chain reaction. The pH/reduction-responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX-loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX-loaded micelles showed retarded drug release in phosphate-buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX-loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual-responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52 , 1771–1780
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