Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Yatao Yin,Chaoping Fu,Mei Li,Xiangpen Li,Mengying Wang,Lei He,Li-Ming Zhang,Ying Peng
Gliomas are the most common and lethal type of primary malignant brain tumor. But the existence of blood brain barrier (BBB) and blood-tumor barrier (BTB) hinder drug from reaching the tumor site. To address this problem, we developed a novel prodrug (Lf-HA-DOX) by conjugating hyaluronic acid with doxorubicin (HA-DOX) by an acid-labile hydrazone linkage, which is released in an acidic environment and accumulates in tumor tissues. Lactoferrin (Lf) was coupled for transporting across the BBB. In vitro, the release of DOX from Lf-HA-DOX was pH-dependent. At lower pH (5.0 and 6.0), the release of DOX was much quicker than that at pH 7.4. In the cellular uptake studies, flow cytometry analyses and confocal laser scanning microscopy results showed significantly enhanced cellular uptake of Lf-HA-DOX and HA-DOX in C6 cells compared to DOX. In BALB/C mice bearing C6 glioma, enhanced accumulation of Lf-HA-DOX in the glioma was observed by real time fluorescence image. Correspondingly, glioma-bearing mice treated with Lf-HA-DOX displayed the longest median survival time, which was 2-fold longer than that of saline group. In conclusion, Lf-HA-DOX was able to significantly increase drug delivery to the glioma, which might provide a promising strategy for antiglioma therapy.
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Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 31
·6356-6365
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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.
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Advanced Healthcare Materials
·
2017
·Vol. 6
·期 19
·1700470
·
IF 5.11
Kai Han,Wei-Yun Zhang,Jin Zhang,Zhao-Yu Ma,He-You Han
Both excess dosages of drug and unwanted drug carrier can lead to severe side effects as well as the failure of tumor therapy. Here, an Fe 3+ –gallic acid based drug delivery system is designed for efficient monitoring of drug release in tumor. Fe 3+ and polyphenol gallic acid can form polygonal nanoscale coordination polymer in aqueous solution, which exhibits certain antitumor effect. Importantly, this coordination polymer possesses extremely high doxorubicin (DOX) loading efficacy (up to 48.3%). In vitro studies demonstrate that the fluorescence of DOX can be quenched efficiently when DOX is loaded on the coordination polymer. The acidity in lysosome also triggers the release of DOX and fluorescence recovery simultaneously, which realizes real-time monitoring of drug release in tumor cells. In vivo studies further indicate that this polyphenol-rich drug delivery system can significantly inhibit tumor growth with negligible heart toxicity of DOX. This system with minimal side effects should be a promising nanoplatform for tumor treatment.
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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.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Xinfeng Cheng,Yong Jin,Tongbing Sun,Rui Qi,Hanping Li,Wuhou Fan
A novel pH and oxidation dual-responsive and injectable supramolecular hydrogel was developed, which was formed from multi-block copolymer poly(ether urethane) (PEU) and α-cyclodextrin (α-CD) inclusion complexes (ICs). The PEU copolymer was synthesized through a simple one-pot condensation polymerization of poly(ethylene glycol), di(1-hydroxyethylene) diselenide, dimethylolpropionic acid and 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate. In aqueous solution, the amphiphilic PEU copolymers could self-assemble into nanoparticles with dual pH and oxidation sensitivities, which can efficiently load and controllably release a hydrophobic drug indomethacin (IND). Then a dual-drug loaded supramolecular hydrogel was obtained by addition of α-CD and hydrophilic model drug (rhodamine B, RB) into the resulting IND-loaded PEU nanoparticle solution. The rheology studies showed that the supramolecular hydrogels with good injectability underwent a pH-induced reversible sol–gel transition and an oxidation-triggered degradation behavior. The in vitro drug release results demonstrated that the hydrogels showed dual drug release behavior and the release rates could be significantly accelerated by addition of an oxidizing agent (H 2 O 2 ) or increasing the environmental pH. Therefore, this injectable and dual stimuli-responsive supramolecular hydrogel based codelivery systems could potentially be a promising candidate for controlled drug delivery systems.
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JOURNAL OF MATERIALS RESEARCH
·
2017
·Vol. 32
·期 4
·717-725
·
IF 1.673
D.D. Men,F. Zhou,H.L. Li,L.F. Hang,X.Y. Li,D.L. Liu,W.P. Cai,L.M. Qi,L.B. Li,Y. Li
A free standing 2D PS colloidal crystal with Au nanoshells/hydrogel composite film (CAuHCF) was fabricated by embedding a 2D PS colloidal crystal with Au nanoshells into a polyacrylic acid (PAA) hydrogel film. This CAuHCF can act as a visualized sensor with high diffraction intensity. The 2D PS colloidal crystal with Au nanoshells was prepared by depositing an Au layer on PS colloidal crystal obtained by interfacial self-assembly. The diffraction intensity of the CAuHCF was increased by about 30-fold than that of traditional 2D PS colloidal crystal/hydrogel composite film on transparent substrate due to large scattering cross section of Au shell. Such sensors based Au nanoshells array with the simple preparation process and the strong diffraction signal are promising ones for practical applications in visual detection. Additionally, with the simple preparation process and high diffraction intensity, other visualized sensors based different hydrogel matrix and the 2D PS colloidal crystal with Au nanoshells could be synthesized for monitoring various analysts.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Jing-Xiao Chen,Yu Shi,Yi-Rang Zhang,Li-Ping Teng,Jing-Hua Chen
In this study, one-pot strategy for the construction of micelles loaded with two types of anticancer drugs (i.e., doxorubicin and methotrexate) together is reported. On the basis of the reaction between boronic acid and 1,2-diol to form boronate ester, the formation of amphiphiles, their self-assembly into micelles and drug encapsulation occurs simultaneously under simple dialysis at the appropriate pH condition. In the one-pot strategy, the micelle yield is high (78.2%) and the drug encapsulation efficiency of the two drugs is improved compared with that of the traditional method. The micelles can selectively increase the drug release ratio at acidic pH, showing the pH-responsive behavior inherited from the property of boronate ester. By combining doxorubicin and methotrexate, the half-maximum inhibition concentrations of the two drugs are obviously reduced, showing synergistic efficacy against cancer cells. This strategy is promising and may be expanded to various applications.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2016
·Vol. 133
·期 39
·
IF 1.866
Lili Yu,Ning Ren,Kuan Yang,Miao Zhang,Li Su
A novel dual-responsive (light and pH) particle based on poly(methacrylic acid), poly(methacrylic acid)–poly[1-(2-nitrophenyl)ethane-1,2-diyl bis(2-methylacrylate)]was prepared with the facile method of two-step homogeneous radical polymerization with methacrylic acid as the monomer and 1-(2-nitrophenyl)ethane-1,2-diyl bis(2-methylacrylate) as a photodegradable crosslinker. Photolytic assessments were conducted upon irradiation with a UV lamp; this led to particle disintegration caused by cleavage of the photolabile crosslinking points. The light-dependent degradation was investigated through particle size changes, absorption spectra variations, surface morphology changes, Fourier transform infrared spectroscopy, and the release of Nile red from the particles after irradiation. The pH dependence of the particle systems induced by the protonation and deprotonation of poly(methacrylic acid) was also confirmed by fluorescence spectroscopy. The triggered release of fluorescein diacetate was investigated to demonstrate that the release behavior in cells was light dependent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 44003.
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POLYMER
·
2016
·
IF 3.586
Xinfeng Cheng,Yong Jin,Rui Qi,Wuhou Fan,Hanping Li,Xiaopeng Sun,Shuangquan Lai
A new diselenide crosslinked polyurethane nanogel was developed, which could respond to pH change and oxidaiton condition. Firstly, PEGylated polyurethane (MPEG-PUBM-MPEG) containing tertiary amino and Br groups was prepared, which can assemble into micelles in aqueous solution. Then the nanogels with diselenides crosslinked polyurethane (PU) core and hydrophilic PEG shell were prepared using sodium diselenide (Na 2 Se 2 ) as a crosslinking agent to react with the Br groups in the PUBM block. The resultant nanogels exhibited enhanced colloidal stability relative to the non-crosslinked micelles, which have a spherical morphology with a diameter about 110–120 nm. Interestingly, the nanogels displayed a pH-induced swelling and oxidation-triggered dissociation behaviors, which can efficiently load indomethacin (IND) drugs and showed an inhibited premature release behavior as compared to the non-crosslinked micelles. An accelerated release behavior at pH 5.0 (54% in 24 h) and a burst release under oxidation condition (95% in 20 h) were observed for the nanogels, indicating their dual pH and oxidation-triggered release behaviors. Considering their enhanced stability, pH-induced swelling and oxidation-triggered degradation characteristics, the diselenide crosslinked nanogels can serve as a potential system for controlled drug delivery.
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ChemCatChem
·
2016
·Vol. 8
·期 21
·3375-3380
·
IF 4.724
Wei-Peng Wu,Yong-Jian Xu,Shang-Wei Chang,Jin Deng,Yao Fu
Graphical Get wet : Full conversion of biomass-derived furfural to furfuryl alcohol and levulinic acid to γ-valerolactone with high turnover frequencies are reached by pH-regulated aqueous catalytic hydrogenation. In addition, the one-pot aqueous reaction of furfural for the preparation of γ-valerolactone is achieved. Semisandwich Ir complexes [Cp*Ir-(di-OMe-bpy)(OH 2 )][SO 4 ] (di-OMe-bpy=4,4′-dimethoxyl-2,2′-bipyridine) and [Cp*Ir-(di-OH-bpy)(OH 2 )][SO 4 ] (di-OH-bpy=4,4′-dihydroxyl-2,2′-bipyridine) are excellent efficient catalysts for the aqueous hydrogenation reactions of biomass carbohydrate derivatives. We show that pH value plays an important role in the hydrogenation reaction. By adjusting the pH value of the solvent, we can improve the catalytic efficiency and control the product distribution. The turnover frequencies (TOF) of hydrogenation of furfural up to 13 877 h −1 and TOF of hydrogenation of levulinic acid up to 12 200 h −1 at 120 °C were achieved. Converting furfural into γ-valerolactone in one step is observed at strong acidic aqueous system, which makes it easy to achieve a distribution-controlled product by pH adjustment.
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MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2016
·Vol. 217
·期 18
·2049-2055
·
IF 2.495
Haibo Wang,Junjie Xiong,Gongyan Liu,Yunbing Wang
A biomimic pH-sensitive polymeric prodrug based on branched polyethylenimine- graft -12-acryloyloxy dodecyl phosphorylcholine and 6-maleimidocaproyl-doxorubicin is rationally designed and successfully synthesized. This polymeric prodrug can spontaneously self-assemble into spherical nanostructures in aqueous solution. The in vitro drug release results imply that this polymeric prodrug can maintain stable in blood circulation while enhance drug release at endosomal acidic condition. Fluorescence microscopy and flow cytometry results demonstrate that the formed prodrug micelles can be internalized by cancer cells effectively. More importantly, this prodrug exhibits excellent cytotoxicity against Hela cells, indicating the pH-sensitive polymeric prodrug micelles can potentially work as a promising platform for efficient cancer therapy.
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LANGMUIR
·
2017
·
IF 3.833
Jian Zhang,Ran Kou,Guangming Liu
Strong polyelectrolyte brushes (SPB) and weak polyelectrolyte brushes (WPB) have different origins with response to pH, which makes their pH-responsive properties sensitive to salt concentration in different ways. Herein, we have employed poly[2-(methacryloyloxy)ethyl trimethylammonium chloride] (PMETAC) and poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) brushes as model systems for SPB and WPB, respectively, to investigate the effect of salt concentration on the pH responses of SPB and WPB using several surface-sensitive techniques. The pH-responsive properties of the PMETAC brushes are governed by the reorganization of the interchain hydrogen bonds between the grafted chains, whereas the pH response of the PDMAEMA brushes is controlled by the charge of the grafted chains. The response of the properties of the PMETAC brushes including hydration, conformation, and surface wettability becomes weaker with increasing salt concentration induced by the competitive adsorption of counterions to the brushes between OH– and Cl–. The weakening of the pH response of the PMETAC brushes is more remarkable at the relatively high pH values. The pH response of the PDMAEMA brushes also exhibits a salt-concentration dependence. As the salt concentration increases, the weakening of the pH response of the PDMAEMA brushes is attributed to the decrease in osmotic pressure within the brushes at relatively low pH values.
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