RSC Advances
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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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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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ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Fanpeng Kong,Yuehui Zhao,Ziye Liang,Xiaojun Liu,Xiaohong Pan,Dongrui Luan,Kehua Xu,Bo Tang
Hydrogen selenide (H2Se) is an important metabolite of dietary Se compounds and has been implicated in various pathological and physiological processes. The development of highly sensitive and selective methods for the sensing of H2Se is therefore very important. Herein, we developed a fluorescent probe (hemicyanine (Hcy)-H2Se) for detecting H2Se based on a new H2Se-specific receptor unit, 1,2-dithiane-4,5-diol. Hcy-H2Se showed high selectivity toward H2Se over thiols (RSH), hydrogen sulfide (H2S), and selenocysteine (Sec) and was further exploited for the fluorescence imaging of H2Se both in living cells and in vivo. Furthermore, with the aid of Hcy-H2Se, we demonstrated that H2Se can be generated and gradually accumulated in HepG2 cells under hypoxic conditions and in the solid tumor after treatment with Na2SeO3.
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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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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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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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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
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2017
·Vol. 52
·期 5
·1176-1184
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IF 1.64
Jing Li,Wenting Shang,Xu Si,Dandan Bu,Padraig Strappe,Zhongkai Zhou,Chris Blanchard
Summary Corn bran polysaccharides were extracted using an ultrasonic-assisted method with a yield of 33.50% and then carboxymethylated. The occurrence of modification was confirmed using Fourier transform infrared spectral analysis. The surface of polysaccharide particles became loosened following the carboxymethylation. The effect of sodium hydroxide concentration, reaction temperature, and the reaction time on the degree of substitution was investigated, and the relationship among the substitution degree, total phenolic content and antioxidant activity were studied. With sodium hydroxide concentration of 6.0 mol L −1 , keeping the reaction temperature of 60 °C and reaction time of 5.0 h, the modified polysaccharides possessed the highest degree of substitution and antioxidant activity. Cell culture model indicated that the carboxymethylated polysaccharide significantly inhibited the proliferation of A549 and HepG-2 cells, and these antitumour characteristics may be associated with the elevated expression of CASP3 , CASP8 , CASP9 , and p53 , as well as the significantly decreased expression of Bcl-2 and iNOS genes. The excellent antioxidant capacity and strong antitumour activity of these polysaccharides might provide a potential application as a naturally functional ingredient.
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MICROCHIMICA ACTA
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2016
·Vol. 183
·期 10
·2823-2830
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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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DYES AND PIGMENTS
·
2017
·
IF 3.473
Guangyang Liu,Xiaodong Huang,Shuning Zheng,Lingyun Li,Donghui Xu,Xiaomin Xu,Yanguo Zhang,Huan Lin
We developed a highly sensitive fluorescent assay based on fluorescence resonance energy transfer (FRET) between gold nanoparticles (AuNPs) and cadmium telluride (CdTe) quantum dots (QDs) for detection of triadimenol in tap water and agricultural irrigation water. The electrostatic interaction between the positively charged CdTe QDs and negatively charged AuNPs strongly quenched the fluorescence emission of CdTe QDs. In the presence of triadimenol, the strong electrostatic attraction between negatively charged AuNPs and positively charged triadimenol molecules rapidly induced the aggregation of AuNPs, blocking the FRET reaction and attenuating the quenched efficiency of CdTe QDs. The change of fluorescence intensity was linearly related to the concentration of triadimenol in the concentration range of 0.338–33.8 μM. The detection limit (S/N = 3) of the sensor was as low as 0.182 μM. The fluorescent sensor was successfully used to detect triadimenol in spiked water samples and gave good recoveries.
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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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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Dujuan Zhao,Huiyuan Zhang,Shengfeng Yang,Wenxiu He,Yuxia Luan
The main cause of multidrug resistance (MDR) is overexpression of active efflux transporters, such as P-glycoprotein (P-gp). To reverse MDR and improve the chemotherapy effect of paclitaxel (PTX), we propose a new drug delivery system based on mixed micelles constructed with d -α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and the mPEG-SS-PTX conjugate with consideration that TPGS is a P-gp inhibitor that can block the cancer cell action of pumping drugs outside of cells and can enhance the anticancer effect. mPEG-SS-PTX is synthesized by conjugating hydrophilic mPEG with a hydrophobic drug, PTX, via a redox-sensitive disulfide bond. The mPEG-SS-PTX conjugate is amphiphilic and can self-assemble in water. Mixed micelles formed by the mPEG-SS-PTX conjugate and TPGS have a low critical micelle concentration (CMC, ∼1.05 × 10 −3 mg/mL) and high drug loading content (∼19.6%). The disulfide bond in the mPEG-SS-PTX conjugate can be broken in cancer cells (a reductive environment) and release PTX to kill cancer cells. In vitro cytotoxicity and cell uptake suggest that mixed micelles can effectively improve the accumulation of PTX in multidrug-resistant MCF-7 cells. Therefore, the present as-prepared mixed micelles very effectively reverse the MDR and enhance the therapeutic effect.
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Small
·
2016
·Vol. 12
·期 46
·6353-6362
·
IF 8.315
Cong Luo,Jin Sun,Bingjun Sun,Dan Liu,Lei Miao,Tyler Jay Goodwin,Leaf Huang,Zhonggui He
The conjugate of paclitaxel (PTX) and docosahexaenoic acid has entered into clinical trials. However, the most recent clinical outcomes fell short of expectations, due to the extremely slow drug release from the hydrophobic conjugates. Herein, a novel prodrug-based nanoplatform self-assembled by the disulfide bond linked conjugates of PTX and oleic acid for rapid and differential release of PTX in tumor cells is reported. This redox-responsive prodrug-nanosystem demonstrates multiple therapeutic advantages, including one-step facile fabrication, high drug-loading efficiency (56%, w/w), on-demand drug release responding to redox stimuli, as well as favorable cellular uptake and biodistribution. These advantages result in significantly enhanced antitumor efficacy in vivo, with the tumor almost completely disappearing in mice. Such a uniquely engineered prodrug-nanosystem has great potential to be used as potent chemotherapeutic nanomedicine in clinical cancer therapy.
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