ACS Applied Materials & Interfaces
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2016
·
IF 7.145
Zhen Zou,Dinggeng He,Linli Cai,Xiaoxiao He,Kemin Wang,Xue Yang,Liling Li,Siqi Li,Xiaoya Su
The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.
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DRUG DELIVERY
·
2016
·
IF 4.843
Daquan Chen,Shengnan Lian,Jingfang Sun,Zongliang Liu,Feng Zhao,Yongtao Jiang,Mingming Gao,Kaoxiang Sun,Wanhui Liu,Fenghua Fu
In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.
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RSC Advances
·
2016
·Vol. 6
·期 34
·28331-28342
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IF 3.289
Lu Wang,Xi Xie,Di Liu,Xiao-Bin Fang,Peng Li,Jian-Bo Wan,Cheng-Wei He,Mei-Wan Chen
Reduction-sensitive micelles with crosslinked cores were developed to load the lipophilic chemotherapeutic drug docetaxel (DTX) in order to overcome the issues of toxicity, water insolubility, and rapid metabolism of DTX. These DTX-loaded micelles (MM(DTX/Crosslink)) provide efficient incorporation and sustained release of DTX. Using independently synthesized LA–PLGA–TPGS and DSPE–PEG polymers as vehicles, MM(DTX/Crosslink) was found to be reduction-responsive, and possessed desirable drug entrapment efficiency (84.17 ± 1.15%) and drug loading efficiency (6.21 ± 0.07%). The MM(DTX/Crosslink) quickly dissociated under reduction conditions that mimicked the reductive intracellular environment, suggesting that it can rapidly release the encapsulated DTX in vitro. Furthermore, to target MM(DTX/Crosslink) to tumors for cancer therapy, iRGD was conjugated to the surface of MM(DTX/Crosslink). The iRGD-MM(DTX/Crosslink) micelles significantly increased the cellular uptake of DTX and inhibited cell proliferation, compared to the micelles without iRGD modification. Moreover, the iRGD-MM(DTX/Crosslink) micelles presented enhanced antitumor effects based on the analyses of apoptosis and cell cycle arrest. The micelles developed in this work may constitute a stable, efficient, and powerful system to deliver DTX into cancer cells.
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JOURNAL OF THE CHINESE CHEMICAL SOCIETY
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2017
·Vol. 64
·期 7
·795-803
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IF 0.935
Junyu Lu,Lianqiang Wei,Dongmei Yao,Xiuju Yin,Hongfang Lai,Xiuxiang Huang
β-AgVO 3 nanorods have been demonstrated to exhibit intrinsic peroxidase-like activity. The oxidation of glucose can be catalyzed by glucose oxidase (GO x ) to generate H 2 O 2 in the presence of O 2 . The β-AgVO 3 nanorods can catalytically oxidize peroxidase substrates including o -phenylenediamine (OPD), 3,3′,5,5′-tetramethylbenzidine (TMB), and diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) by H 2 O 2 to produce typical color reactions: OPD from colorless to orange, TMB from colorless to blue, and ABTS from colorless to green. The catalyzed reaction by the β-AgVO 3 nanorods was found to follow the characteristic Michaelis–Menten kinetics. Compared with horseradish peroxidase and AgVO 3 nanobelts, β-AgVO 3 nanorods showed a higher affinity for TMB with a lower Michaelis–Menten constant ( K m ) value (0.04118 mM) at the optimal condition. Taking advantage of their high catalytic activity, the as-synthesized β-AgVO 3 nanorods were utilized to develop a colorimetric sensor for the determination of glucose. The linear range for glucose was 1.25–60 μM with the lower detection limit of 0.5 μM. The simple and sensitive GO x -β–AgVO 3 nanorods–TMB sensing system shows great promise for applications in the pharmaceutical, clinical, and biosensor detection of glucose.
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ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Meng-Yun Peng,Di-Wei Zheng,Shi-Bo Wang,Si-Xue Cheng,Xian-Zheng Zhang
A multifunctional nanosystem based on two-dimensional molybdenum disulfide (MoS2) was developed for synergistic tumor therapy. MoS2 was stabilized with lipoic acid (LA)-modified poly(ethylene glycol) and modified with a pH-responsive charge-convertible peptide (LA-K11(DMA)). Then, a positively charged photosensitizer, toluidine blue O (TBO), was loaded on MoS2 via physical absorption. The negatively charged LA-K11(DMA) peptide was converted into a positively charged one under acidic conditions. Charge conversion of the peptide could reduce the binding force between positively charged TBO and MoS2, leading to TBO release. Furthermore, the positively charged nanosystem was easily endocytosed by cells. Photo-induced hyperthermia of MoS2 in the tumor areas could promote TBO release and exhibited photothermal therapy. In vitro and in vivo results demonstrated that fluorescence and photo-induced reactive oxygen species (ROS) generation of TBO were severely decreased by MoS2 under normal conditions. While in the acidic condition, the pH-responsive nanosystem exhibited a highly specific and efficient antitumor effect with TBO release and photo-induced ROS generation, suggesting to be a promising accessory for synergistic tumor therapy.
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JOURNAL OF MATERIALS SCIENCE
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2016
·Vol. 51
·期 20
·9367-9383
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IF 2.302
Chen Fangfang,Chen Heng,Duan Xiao,Jia Jiqiong,Kong Jie
In this contribution, we reported a novel strategy to synthesize porous molecularly imprinted polymers (MIPs) of anticancer drug of doxorubicin hydrochloride (DOX) using reduction-cleavable hyperbranched polymers containing disulfide bonds (ds-HP-alkyne). The porous MIPs (MIP-DOX-HP) possess enhanced specific surface area and porosity by the incorporation of cleavable hyperbranched polymers from the copper(I)–catalyzed azide–alkyne click chemistry. In comparison to MIPs synthesized without using ds-HP-alkyne, MIP-DOX-HP exhibits more regular and open porous structures, which increase the loading and controlled release abilities of DOX anticancer drug. Under optimized pH condition, the total cumulative release amount of DOX at equilibrium is as high as 2134 and 1249 µg for MIP-DOX-HP and MIP-DOX, respectively. The effective and robust strategy for synthesizing MIPs using cleavable hyperbranched polymers is helpful for extending applications of MIPs in drug delivery and target-activated release systems.
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RSC Advances
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2016
·Vol. 6
·期 104
·102398-102405
·
IF 3.289
Yuxi Liu,Siwen Li,Dan Chen,Zhaohui Wang,Jinnan Zhang,Caiping Tian,Li Ding,Yaqi Chen,Zhiyu Qian,Yueqing Gu
The existence of EML4–ALK, a mutated fusion gene in non-small-cell lung cancer (NSCLC), is an important consideration in the decision of the treatment options for NSCLC patients. However, there has been no standardized methods for EML4–ALK fusion gene detection up to now, which makes the development of novel detection probes particularly appealing. A molecular beacon is effective in detecting the level of a particular mRNA in living cells with easy signal visualization and convenient application. In this study, a molecular beacon composed of a gold nanoparticle core densely packed with FITC-labeled hairpin DNA sequences was synthesized and characterized. The presence of the EML4–ALK fusion gene will specifically open the hairpin structure, leading to the recovery of FITC fluorescence. This molecular beacon could precisely distinguish NSCLC cell lines with different levels of EML4–ALK mRNA expression, as indicated by obvious fluorescence in the EML4–ALK positive H2228 cell line and a negligible signal in the negative A549 cell line. The sensitivity and specificity of the molecular beacon were further verified in H2228 cells treated with small interfering RNAs (siRNAs) against ALK, which demonstrated decreased fluorescence after gene silencing. These results were simultaneously confirmed by flow cytometry and Q-PCR. More importantly, our molecular beacon successfully identified the EML4–ALK fusion gene in tissue specimens from 2 of 23 NSCLC patients. The results were consistent with Q-PCR quantification. Therefore, this molecular beacon holds great potential in clinical diagnosis of the EML4–ALK fusion gene with remarkable sensitivity and convenience.
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高影响因子
DRUG DELIVERY
·
2016
·
IF 4.843
Qing Chang,Rui Geng,Shanzheng Wang,Ding Qu,Xiangfei Kong
Treatment for multiple myeloma (MM) with a combined strategy of bone and tumor targeting remains a crucial technical challenge due to the incorporation of various functional components into one single system. Here, we developed dioleoyl phosphatidic acid (DOPA)-based paclitaxel (PTX)-loaded liposomes with modifications of alendronate and transferrin (Ald-/Tf-modified PTX-L), which were capable of bone affinity mediated by phosphate groups in DOPA and alendronate, and tumor targeting offered by transferrin. Ald-/Tf-modified PTX-L had clear and well-defined spherical shape with an intermediated size of 118.8 ± 4.8 nm, a highly negative surface charge of −46.9 ± 6.8 mV and a drug entrapment efficiency (DEE) of approximately 80%. When the pH was changed from pH 7.4 to pH 6.5, the accumulative release of PTX from Ald-/Tf-modified PTX-L significantly increased from 26.7 ± 3.7% to 41.7 ± 4.9%. Importantly, liposomes based on DOPA displayed an obviously stronger affinity with hydroxyapatite (HAp) than 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-based liposomes. Compared to PTX-L, Ald-/Tf-modified PTX-L exhibited obvious improvement of cytotoxicity (IC50 = 1.25 ± 0.09 μg/mL), significant enhancement on PTX intracellular accumulation (16.58 ± 0.62 μg/mg) and notable promotion to apoptosis induction (45.21 ± 3.10%) toward myeloma (MM1s) cells. In this study of antitumor efficacy, Ald-/Tf-modified PTX-L with bone-specific targeting showed a significant effect on extending the median survival time (48 days) and terminal survival time (> 58 days) against the MM1S-injected nude mice among all formulations. The results suggested that Ald-/Tf-modified PTX-L had potential as an efficient anticancer drug delivery system for MM therapy.
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CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Xueqian Wang,Mengliu Zhang,Dawei Zhang,Shumei Wang,Chunyan Yan
Osteoporosis is characterized by a reduction in bone mass and bone mineral density, which weakens the bone. Due to the side effects associated with drugs that are currently used to treat this disease, an increasing number of studies have focused on the research of effective ingredients derived from natural products. In particular, polysaccharides extracted from Chinese herbal medicines have received increasing attention. In this study, we isolated a homogeneous polysaccharide (COP90-1) from the dried rhizomes of Curculigo orchioides , a famous traditional Chinese medicine that is widely used in China, and determined its structure using the combined methods of chemical and spectral analyses. In addition, its effects on the proliferation and differentiation of primary mouse osteoblasts were assessed. The results showed that COP90-1 can effectively promote the proliferation and differentiation of primary osteoblasts in vitro . Additional studies are warranted to study the effects of this compound in vivo .
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DALTON TRANSACTIONS
·
2017
·Vol. 46
·期 19
·6425-6432
·
IF 4.029
Yuling Liu,Qingsheng Wu,Yaping Zhao
1D Ag3PO4-NPs/Cu-NWs have been constructed to enhance visible-light-driven photocatalytic activity via biomimetic synthesis. Cu nanowires (NWs) were synthesized by a facile hydrothermal method. During the process of biomimetic synthesis, the porous PTFE film, which can mimic the transport process of cell membranes, plays an important role in controlling the transport speed of silver ions (Ag+) to decrease the reaction speed. Thus inhibition of the replacement reaction of Ag+/Cu and the uniform growth of Ag3PO4 nanoparticles (NPs) with a diameter of about 10 nm on Cu-NWs can be realized simultaneously. The diameter of Ag3PO4-NPs/Cu-NW is about 70 nm. Owing to the high electron transport of single crystal Cu-NWs, the free electrons in Ag3PO4 are transferred out to promote photogenerated electron–hole pair separation. The stability of Ag3PO4 NPs of the Ag3PO4-NPs/Cu-NWs was improved and the photodecomposition no longer occurred. Meanwhile, the band-gap of Ag3PO4 decreased to 2.07 eV after being coated on Cu-NWs and expanded the absorption scope of visible-light. In addition, the active species-trapping experiments indicated that the holes and ˙O2− play important roles in the photocatalytic reactions. The novel Ag3PO4-NPs/Cu-NWs were used for the degradation of ciprofloxacin (CPFX) for the first time and showed high photocatalytic degradation performance. After visible-light irradiation for 15 min, the degradation rates of CPFX with pure Ag3PO4 NPs and AC0.3 as catalysts were about 27% and 53%. In the end, the degradation efficiency of Ag3PO4-NPs/Cu-NWs was 6.07 times that of the pure Ag3PO4 NPs.
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MICROCHIMICA ACTA
·
2016
·Vol. 183
·期 10
·2823-2830
·
IF 4.831
Zhong Yaping,Deng Chun,He Yu,Ge Yili,Song Gongwu
The authors describe a method for increasing the peroxidase-like catalytic properties of copper nanoclusters (Cu-NCs) that are used in non-enzymatic assays. The Cu-NCs were prepared by utilizing 6-thio-β-cyclodextrin as both the template and as effective modulators for increasing the peroxidase-like properties of the Cu-NCs. The β-CD-coated Cu-NCs have an average diameter of 2 nm, are stable in aqueous solutions, display strong fluorescence with excitation/emission peak wavelengths of 360/450 nm, and possess peroxidase-like catalytic activity which makes them a useful enzyme mimic. We have applied the findings to non-enzymatic photometric determination (at 650 nm) of (a) H 2 O 2 in the concentration range of 0.02 to 10 mM using the β-CD/Cu-NC assisted oxidation of tetramethylbenzidine by H 2 O 2 , and (b) glucose in the concentration range of 0.04 to 20 mM after addition of glucose oxidase and formation of H 2 O 2 . The detection limits (at an S/N ratio of 3) are 0.2 μM for H 2 O 2 and 0.4 μM for glucose. The β-CD coating is found to result in a strong increase in the reaction rate, probably because the cavity of β-CD acts as a pocket for the recognition and catalysis of substrate. Hence, the binding specificity becomes similar to that of natural enzymes.
The peroxidase-like catalytic activity of Cu-NCs in non-enzymatic sensors is strongly enhanced by utilizing mono-6-thio-β-cyclodextrin (mono-6-SH-β-CD) as both the template molecule and the effective rate modulator.
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ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
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