Biomaterials Science
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2015
·Vol. 4
·期 2
·338-345
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IF 3.831
Sheng Wang,Weitao Yang,Jing Cui,Xue Li,Yan Dou,Lin Su,Jin Chang,Hanjie Wang,Xiaodong Li,Bingbo Zhang
The side effects of antitumor drugs and low treatment efficacy are two major challenges of current chemotherapy. To address these issues, we developed a new kind of smart nanocarriers that combine pH-responsive chemotherapy and near-infrared (NIR) light triggered photodynamic therapy. These nanocarriers were based on upconversion nanoparticle (UCN)-loaded folate-conjugated polymeric lipid vesicles (UFPLVs). Merocyanine 540 (MC540), as a photosensitizer, was loaded in the UFPLVs; doxorubicin hydrochloride (DOX), as an antitumor drug, was conjugated to the surfaces of UFPLVs by pH-sensitive hydrazone bonds. The newly developed MC540&DOX–UFPLVs had a nanosized structure with targeting ligand modification, so they had the potential to accumulate into tumor sites via a combination of passive and active targeting effects. An in vitro singlet oxygen test showed that the nanocarriers can generate cytotoxic singlet oxygen successfully under the irradiation of NIR light. In vitro DOX release profiles demonstrated that the nanocarriers can achieve a pH-triggered drug release. It has been demonstrated by a cellular uptake study that the nanocarriers can efficiently deliver drugs and photosensitizers into tumor cells. In vitro and in vivo combination treatments evidenced the high antitumor effects of MC540&DOX–UFPLVs under NIR light irradiation. These results suggest that the MC540&DOX–UFPLVs may be promising nanocarriers for tumor combination therapy applications.
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Journal of Materials Chemistry B
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2015
·Vol. 3
·期 48
·9383-9396
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IF 4.726
Xin Liang,Ying Yang,Lijun Wang,Xianbing Zhu,Xiaowei Zeng,Xiaojin Wu,Hongbo Chen,Xudong Zhang,Lin Mei
Poly(lactide-co-glycolide) (PLGA)-based particles have been widely used as carriers of various kinds of drugs, which are sequestered by the cell membrane and degraded through endo-lysosome and auto-lysosomal pathways. Lysosome is the destination of endocytosis and autophagy, which is also an organelle for the cell to execute death. Here, we show that chloroquine (CQ) and ciprofloxacin (CPX) (LMP inducer reagents)-loaded PLGA hollow microspheres (HMs) could be delivered by passive targeting into endo-lysosome and auto-lysosome. Co-loading with NaHCO3 accelerates the release of CQ and CPX in the acid environment of endo-lysosome and auto-lysosome. Subsequently, the released CQ and CPX induce lysosomal membrane permeabilization (LMP), which leads to cancer cell death in three different manners: apoptosis, autophagic cell death and apoptosis with autophagosome. Moreover, we use rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR), to induce autophagy and inhibit cell growth. Rapamycin–NaHCO3-loaded HMs combined CQ–NaHCO3-loaded HMs could efficiently induce cancer cell death through apoptosis with autophagosome both in vitro and in vivo.
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APPLIED CLAY SCIENCE
·
2015
·
IF 2.467
Honghai Wu,Hanrui Xie,Guangping He,Yufeng Guan,Yanlin Zhang
Tetracycline frequently needs to be detected in the environment; therefore, iron-intercalated montmorillonite (Fe-Mt) was evaluated as a model adsorbent to evaluate tetracycline adsorption behavior . The Fe-Mt sample derived from Na + -montmorillonite (Mt) by the introduction of iron-(hydr)oxides was fully characterized using the techniques of XRD , FTIR , TEM, and SEM as well as N 2 -adsorption/desorption methods. The delaminated structure of Fe-Mt could cause remarkable increases in both the surface area and pore volume. Fe-Mt also showed remarkably distinct behavior from Mt for TC adsorption. The TC adsorption by Fe-Mt was found to be highly influenced by the pH as well as the types and concentrations of background electrolytes. The positive effect of anions on the TC adsorption by Fe-Mt at acidic pH values follows the following adsorption maximum order: PO 4 3 − > SO 4 2 − » NO 3 − > Cl − > ClO 4 − . The solution pH affects the TC adsorption, and the adsorption maximum occurs at a pH around 5.0. The Langmuir and Freundlich equations were shown to fit well to the TC adsorption isotherms on Fe-Mt, and the former equation was a better fit. These adsorption-related performances could be ascribed to Fe-Mt having formed characteristic bulk/surface/pore structures. The multiple potential coexisting efficient mechanisms or pathways responsible for the TC adsorption by Fe-Mt were finally proposed and discussed in comparison with Mt and ferrihydrite .
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Materials Science & Engineering C-Materials for Biological Applications
·
2014
·
IF 2.736
Juan Huang,Yanan Xue,Ning Cai,Han Zhang,Kaikai Wen,Xiaogang Luo,Sihui Long,Faquan Yu
To reduce leakage on the drug-delivery pathway to minimize side effect of reduction or pH sensitive drug delivery systems, we designed a glutathione (GSH)/pH co-triggered magnetic nanogel drug delivery system for doxorubicin (DOX) based on the GSH concentration and pH difference between intracellular and extracellular environments. The introduction of superparamagnetic iron oxide nanoparticles (SPION) was intended for magnetic targeting. The magnetic DOX-loaded nanogel was then prepared by the oxidation of thiolated alginate with thiolated SPION in the presence of DOX. The nanogel size can be readily regulated in a range of 120–320 nm upon preparation conditions, with a negative surface charge of around − 40 mV. Saturation magnetization was estimated at 27.4 emu/g Fe by VSM. In vitro release was conducted in simulated cancerous environment conditions such as a high GSH concentration and mild acidity. As a result, the nanogel expressed, upon dual stimuli of pH 5/10 mM GSH, significantly higher accumulative release than upon single stimulus of pH 5 without GSH or pH 7.4/10 mM GSH. In vitro cytotoxicity against HeLa cells clearly illustrated that the nanogel could effectively inhibit cell growth, and the IC 50 was figured out to be 2.3 μg/mL of the nanogel, while the nanogel exclusive of DOX was nontoxic. Confocal laser scanning microscopy observation, combined with the result of Prussian blue staining, indicated that DOX was efficiently internalized into HeLa cells through endocytosis, released into the cytoplasm, and then principally entered the nuclei. The quantitative examination of the iron content revealed an exponential increase in the cellular uptake and an exponential decrease in the uptake efficiency with the fed nanogel. This drug-loaded nanogel could be a promising drug carrier for effective tumor-targeted chemotherapy.
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BIOMACROMOLECULES
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2013
·
IF 5.371
Jie Ren,Yanxin Zhang,Ju Zhang,Hongjun Gao,Gan Liu,Rujiang Ma,Yingli An,Deling Kong,Linqi Shi
Herein, a series of biocompatible, robust, pH/sugar-sensitive, core-cross-linked, polyion complex (PIC) micelles based on phenylboronic acid–catechol interaction were developed for protein intracellular delivery. The rationally designed poly(ethylene glycol)-b-poly(glutamic acid-co-glutamicamidophenylboronic acid) (PEG-b-P(Glu-co-GluPBA)) and poly(ethylene glycol)-b-poly(l-lysine-co-ε-3,4-dihydroxyphenylcarboxyl-l-lysine) (PEG-b-P(Lys-co-LysCA)) copolymers were successfully synthesized and self-assembled under neutral aqueous condition to form uniform micelles. These micelles possessed a distinct core-cross-linked core–shell structure comprised of the PEG outer shell and the PGlu/PLys polyion complex core bearing boronate ester cross-linking bonds. The cross-linked micelles displayed superior physiological stabilities compared with their non-cross-linked counterparts while swelling and disassembling in the presence of excess fructose or at endosomal pH. Notably, either negatively or positively charged proteins can be encapsulated into the micelles efficiently under mild conditions. The in vitro release studies showed that the release of protein cargoes under physiological conditions was minimized, while a burst release occurred in response to excess fructose or endosomal pH. The cytotoxicity of micelles was determined by cck-8 assay in HepG2 cells. The cytochrome C loaded micelles could efficiently delivery proteins into HepG2 cells and exhibited enhanced apoptosis ability. Hence, this type of core-cross-linked PIC micelles has opened a new avenue to intracellular protein delivery.
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Polymer Chemistry
·
2015
·Vol. 6
·期 11
·2069-2075
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IF 5.52
Fan Jia,Yin Wang,Haibo Wang,Qiao Jin,Tongjiang Cai,Yangjun Chen,Jian Ji
Ideal drug delivery systems are required to be stable in circulation, while instable at targeted sites to induce rapid drug release. To address this dilemma, novel light cross-linkable and pH de-cross-linkable micelles were developed as drug nanocarriers. Poly(ethylene glycol)-poly-(hydrazone umbelliferone)-aspartamide (mPEG-OMC) with light responsive coumarin moieties and pH responsive hydrazone groups in the side chains was synthesized. The polymers can self-assemble into micelles, which can be conveniently stabilized via UV-light induced cross-linking based on the dimerization of coumarin moieties. While under slight acidic conditions, the cross-linked micelles can also be de-cross-linked by the cleavage of hydrozone bonds in the cross-linking segments, accelerating the release of encapsulated drugs. Thus the benefits of pH and light stimuli-responsiveness can be combined and their disadvantages are avoided. The doxorubicin-loaded micelles showed high mortality towards HepG2 cells. We have demonstrated the UV light cross-linkable micelles with pH-triggered de-cross-linking properties as a new approach for designing smart drug delivery systems.
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Polymer Chemistry
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2013
·Vol. 4
·期 15
·4092-4102
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IF 5.231
Qijing Chen,Xueteng Cao,Hao Liu,Wei Zhou,Lianjie Qin,Zesheng An
Well-defined core cross-linked star (CCS) polymers of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) were prepared via cross-linking copolymerization in an aqueous-based dispersion polymerization system, mediated by reversible addition–fragmentation chain transfer (RAFT) polymerization. The synthesized CCS polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), dynamic light scattering (DLS), and conductivity and zeta potential measurements. The use of PDMAEMA CCS polymers as effective emulsifiers for oil-in-water emulsions was investigated. Interfacial tension measurements showed that the CCS polymer reduced the interfacial tension between water and oil in a pH-dependent manner. Gelled high internal phase emulsions (HIPEs) were formed at high oil fractions (80–89 vol%) and over a wide range of pH values (2–12). The HIPEs were characterized by conductivity, confocal laser scanning microscopy (CLSM) and rheology. The emulsion properties in terms of oil droplet size, long-term stability and rheology were pH-dependent. Complete demulsification of HIPEs was easily realized 2 min after the addition of base. The CCS-stabilized HIPEs were used as templates to prepare porous hydrophilic polymers by polymerizing the monomers in the continuous aqueous phase. The study presented herein reveals that responsive CCS polymers can be used as effective stabilizers for the formation of responsive HIPEs, which have a wide range of applications.
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BIOMACROMOLECULES
·
2013
·
IF 5.371
Yue Huang,Zhaohui Tang,Xuefei Zhang,Haiyang Yu,Hai Sun,Xuan Pang,Xuesi Chen
A series of pH-responsive random copolymer poly(l-glutamic acid-co-l-lysine) [P(Glu-co-Lys)] were synthesized through the ring-opening polymerization (ROP) of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) and 3-benzyloxycarbonyl-l-lysine N-carboxyanhydride (ZLys-NCA) and the subsequent deprotection. The chemical structure of the P(Glu-co-Lys)s was confirmed by NMR. Critical aggregation concentration and transmission electron microscopy measurements indicated that the P(Glu-co-Lys)s could self-assemble into aggregates in phosphate buffer. The surface charge of P(Glu-co-Lys) aggregates was greatly affected by the solution’s pH and l-glutamic acid/l-lysine ratio because the carboxyl and amino groups present on the P(Glu-co-Lys) aggregates could be protonated or deprotonated to become charged. The pH value of the solution at which the surface charge of the P(Glu-co-Lys) aggregates reversed could be manipulated by the feed ratio of BLG-NCA and ZLys-NCA. In vitro methyl thiazolyl tetrazolium assays demonstrated that negatively charged P(Glu-co-Lys)s were nontoxic and biocompatible. Positive charged P(Glu-co-Lys)s showed some cytotoxicity to Hela cells. Cisplatin (CDDP) was used as a model anticancer drug to evaluate the charge-reversal drug delivery system. By the manipulation of CDDP loading content, the surface charge of the CDDP/P(Glu-co-Lys) nanoparticles could be reversed to positive from negative at tumor extracellular pH (pHe 6.5–7.2). An enhanced drug uptake and inhibition of cancer cell proliferation were observed for the tumoral pHe triggered charge-reversal CDDP/P(Glu-co-Lys) drug delivery system. These indicated that the CDDP/P(Glu-co-Lys) nanoparticles could be used as intelligent drug delivery systems for cancer therapy.
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ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Liangliang Dai,Qingfeng Zhang,Jinghua Li,Xinkun Shen,Caiyun Mu,Kaiyong Cai
In this work, we employed dendrimerlike mesoporous silica nanoparticles with hierarchical pores (HPSNs) to fabricate drug delivery system bioimaging and targeted tumor therapy in vivo. N,N-phenylenebis(salicylideneimine)dicarboxylic acid (Salphdc) was used both as the gatekeeper of HPSNs via pH-responsive coordination bonds between −COOH of Salphdc and In3+ ions and as a fluorescence imaging agent. Folic acid was then conjugated to Salphdc as the targeting unit. The results revealed that the system could deliver model drug DOX to the tumor site with high efficiency and then cause cell apoptosis and tumor growth inhibition. Moreover, the conjugated Salphdc was proved to be a promising fluorescence probe for tracing distribution of the system in vivo. The study affords a potential nanoconainer for cancer therapy and biological imaging.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2014
·
IF 4.287
Mengtan Cai,Mengtian Leng,Aijing Lu,Liu He,Xiaoxiong Xie,Lei Huang,Yuhao Ma,Jun Cao,Yuanwei Chen,Xianglin Luo
Amphiphilic poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacrylate-N,N-diethylammonium-betaine) (PCL-SS-PDEASB) was designed and synthesized successfully. pH and redox dually responsive micelles were prepared based on the obtained copolymers, with zwitterionic sulfobetaines as hydrophilic shell, DEA as pH sensitive content and disulfide as redox responsive linkage. The micelle diameters were all less than 200 nm and the micelle diameter distributions were narrow. These micelles could be triggered by pH and redox condition. The drug release from the drug-loaded micelles displayed fastest under simultaneously acidic and reductive conditions. Results of in vitro cell toxicity evaluation showed that introduction of sulfobetaines could greatly decrease the toxicity of poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate) (PCL-SS-PDEA) micelles. DOX-loaded PCL-SS-PDEASB micelles showed higher efficiency to kill HeLa cells than DOX-loaded PCL-PDEASB micelles. Half inhibitory concentration (IC 50 ) of DOX-loaded PCL-SS-PDEASB micelles decreased with the content of sulfobetaines increasing and was even closer to that of DOX·HCl. Thus, the pH and redox dually responsive biodegradable micelles generated by PCL-SS-PDEASB may be potential smart drug carriers for tumor targeted delivery.
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CHEMICAL ENGINEERING JOURNAL
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2017
·
IF 6.216
Yuanyuan Li,Xueqing Qiu,Yong Qian,Wenlong Xiong,Dongjie Yang
We developed a simple and practical method to prepare pH-responsive lignin-based complex micelles in green solvents using purified alkali lignin. Alkali lignin (AL) was quaternized and further self-assembled into lignin-based complex micelles with sodium dodecyl benzenesulfonate (SDBS) in an ethanol/water mixture. The FT-IR and 1 H NMR spectra indicated the successful grafting of quaternary ammonium groups on AL. TEM images showed that the complex micelles were uniform spherical nanoparticles. The complex micelles also exhibited rich phase behaviors responding to pH changes. Ibuprofen (IBU) was used as a drug model and more than 74.44% could be encapsulated via hydrophobic interactions. The in vitro release behavior of IBU was pH-dependent and exhibited controlled release properties. Therefore, more than 75% of IBU could be preserved in simulated gastric fluid (SGF, pH 1.2), and over 90% could be released smoothly in simulated intestinal fluid (SIF, pH 7.4). This work suggests a novel strategy for fabricating an oral drug delivery carrier and is of significance for the value-added utilization of lignin.
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Acta Biomaterialia
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2017
·
IF 6.319
Jiao Guan,Zun-Qiang Zhou,Mao-Hua Chen,Hui-Yan Li,Da-Nian Tong,Jun Yang,Jing Yao,Zheng-Yun Zhang
In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. In this system, FA was attached to the terminal of the hydrophilic segment of poly(lactic acid)–poly( L -lysine) (PLA–PLL), and PLL was modified by a citric acid group. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency. Statement of significance Negatively charged nano-carriers prolonged anti-cancer drugs’ blood circulation. However it is difficult to be internalised. Therefore, a negative-to-positive charged micelle surface could improve selectivity for tumour cells and increase uptake chance. In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency.
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