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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2018 ·Vol. 19 ·期 10 ·3132 · IF 3.687

Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

Liang Li,Na Liang,Danfeng Wang,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun

The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10−3mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.Keywords:chitosan;deoxycholic acid;folic acid;amphiphilic polymer;micelles;paclitaxel

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SENSORS AND ACTUATORS B-CHEMICAL · 2015 · IF 4.097

Delicate photoelectrochemical sensor for folic acid based on carbon nanohorns supported interwoven titanate nanotubes

Hong Dai,Yilin Li,Shupei Zhang,Lingshan Gong,Xiuhua Li,Yanyu Lin

Herein, a signal-amplified photoelectrochemical sensing platform based on interwoven titanate nanotubes and carbon nanohorns conjugates was constructed for folic acid determination. Specifically, titanate nanotubes with reticulation structure were employed as optoelectronic element, which possessed fine photocatalytic activity and enhancement in facilitating fast and long-distance electron transport. Hierarchical-structured carbon nanohorns were introduced as the mainstay to provide as the electron-transport medium to capture and transmit electrons from excited titanate nanotubes to the sensing matrix owing to the prominent conductivity and large surface. Furthermore, the holes from valence band of stimulated titanate nanotubes could transfer to their surface and be consumed by folic acid, thus enhancing the photocurrent response. Hence, under the optimal conditions, a linear relationship between photocurrent increase and logarithm concentration of folic acid was obtained in the wide range from 1   ×   10 −10 to 5   ×   10 −5 M with a detection limit of (2.5   ±   0.005)   ×   10 −11 M. The well-designed transducer showed practical advantages, such as universality, simplicity and convenience, opening up a valuable application for other important molecules assessment.

CAS / MDL: 59-30-3
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Analytical Methods · 2015 ·Vol. 7 ·期 13 ·5419-5427 · IF 1.821

A novel electrochemical aptasensor based on MWCNTs–BMIMPF6 and amino functionalized graphene nanocomposite films for determination of kanamycin

Xiaoli Qin,Wenjuan Guo,Huijing Yu,Juan Zhao,Meishan Pei

A simple electrochemical sensor based on a novel composite film consisting of multi-walled carbon nanotubes (MWCNTs), a room temperature ionic liquid (RTIL) of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), and amino functionalized graphene (GR–CO–NH–CH2–CH2–NH2) was constructed for the detection of kanamycin. Firstly, MWCNTs–BMIMPF6 composites were fabricated on the surface of a glass carbon electrode (GCE). The synergy mechanism between the MWCNTs and RTIL has been discussed. Secondly, GR–CO–NH–CH2–CH2–NH2 was modified on the first film, which could greatly improve the conductivity of the electrode. The structure of the resultant graphene oxide (GO) was confirmed by FTIR and SEM. The properties of the aptasensor were characterized by electrochemical methods. Under the optimum conditions, the electrochemical aptasensor exhibited a wide linear range for kanamycin from 0.001 to 100 μM with a low limit of detection of 0.87 nM (S/N = 3). The as-prepared aptasensor showed high sensitivity, reproducibility and stability. Finally, the proposed electrochemical aptasensor was successfully applied for the detection of kanamycin in a real sample.

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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Fabrication of Multifunctional SiO2@GN-Serum Composites for Chemo-Photothermal Synergistic Therapy

Yuwei Liu,Jing Bai,Xiaodan Jia,Xiue Jiang,Zhuo Guo

Recently, the chemo-photothermal synergistic therapy has become a potential method for cancer treatment. Herein, we developed a multifunctional nanomaterial for chemo-photothermal therapeutics based on silica and graphene core/shell structure (SiO2@GN) because of the ability of GN to convert light energy into heat. Serum protein was further modified onto the surface of GN (SiO2@GN-Serum) to improve the solubility and stability of GN-based nanoparticles in physiological conditions. The as-synthesized SiO2@GN-Serum nanoparticles (NPs) have been revealed to have high photothermal conversion efficiency and stability, as well as high storage and release capacity for anticancer drug doxorubicin (SiO2@GN-Serum-Dox). The therapeutic efficacy of SiO2@GN-Serum-Dox has been evaluated in vitro and in vivo for cervical cancer therapy. In vitro cytotoxicity tests demonstrate that SiO2@GN-Serum NPs have excellent biocompatibility. However, SiO2@GN-Serum-Dox NPs show higher cytotoxicity than SiO2@GN-Serum and free Dox under irradiation with NIR laser at 1.0 W/cm2 for 5 min owing to both SiO2@GN-Serum-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, the tumor growth is significantly inhibited by chem-photothermal effect of SiO2@GN-Serum-Dox. Overall, compared with single chemotherapy or photothermal therapy, the combined treatment demonstrates better therapeutic efficacy. Our results suggest a promising GN-based core/shell nanostructure for biomedical applications.

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Journal of Materials Chemistry B · 2015 ·Vol. 3 ·期 8 ·1667-1676 · IF 4.726

Controlled release and corrosion protection by self-assembled colloidal particles electrodeposited onto magnesium alloys

Jiadi Sun,Ye Zhu,Long Meng,Wei Wei,Yang Li,Xiaoya Liu,Yufeng Zheng

We report a potential example of using surface functionalization to provide magnesium alloys (Mg–Ca) with controlled release and corrosion resistance properties. A key feature of this approach is to treat the Mg–Ca surfaces with nanoparticles via electrodeposition that can stably load and controllably release bioactive agents or drugs. These photo-cross-linkable and nano-scale particles were prepared by the self-assembly of an amphiphilic poly(γ-glutamic acid)-g-7-amino-4-methylcoumarin (γ-PGA-g-AMC) with encapsulation of a vitamin; moreover, the size and morphology of the resulting particles were studied. Fluorescence microscopy analysis indicated that Vm was effectively incorporated into the γ-PGA-g-AMC particles. Scanning electron microscopy (SEM) images showed that the colloidal particles could be uniformly electrodeposited on the Mg–Ca alloys. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses confirmed the successful anchoring of the particles. After the surface electrodeposition of self-assembled colloidal particles, the in vitro degradation results show that deposition of the particles was found to reduce the degradation rate of the magnesium alloys; moreover, the vitamin was controllably released for up to 20 days. Furthermore, the Mg–Ca substrate functionalized with colloidal particles containing a vitamin significantly promoted the attachment, proliferation and spread of NIH-3T3 normal cells. The entire strategy may be used in various medical devices to create coatings for improved biomedical performance.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2014 · IF 5.9

Rational Design of Cancer-Targeted BSA Protein Nanoparticles as Radiosensitizer to Overcome Cancer Radioresistance

Yanyu Huang,Yi Luo,Wenjie Zheng,Tianfeng Chen

Radiotherapy displays curative potential for cervical cancer management, but radioresistance occurs during long-term therapy. To overcome this limitation, tumor-targeted nanotechnology has been proposed to enhance the radiosensitivity of solid tumors. Herein, we used biocompatible bovine serum albumin nanoparticles (BSANPs) as carriers of organic selenocompound (PSeD) with folate (FA) as the targeting ligand to fabricate a cancer-targeted nanosystem. The combination of PSeD and BSANPs endowed the nanosystem with higher light absorption and reactive oxygen species (ROS) generation owing to their properties of surface plasmon resonance (SPR) effect, heavy metal effect, high refractive index and nanoparticulate interfacial effect. The combined treatment drastically increased the ROS overproduction, VEGF/VEGFR2 inactivation and inhibition of XRCC-1-mediated repair of DNA damage, thus triggering G2/M phase arrest and apoptosis. Taken together, our findings demonstrate the utility of FA-BSANPs as a promising radiosensitizer to improve cancer radiotherapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2013 ·Vol. 2 ·期 10 ·1379-1389 · IF 0

Engineered design of theranostic upconversion nanoparticles for tri-modal upconversion luminescence/magnetic resonance/X-ray computed tomography imaging and targeted delivery of combined anticancer drugs

Gan Tian,Wenyan Yin,Junjiang Jin,Xiao Zhang,Gengmei Xing,Shoujian Li,Zhanjun Gu,Yuliang Zhao

Upconversion nanoparticles (UCNPs) are ideal building blocks for fabricating multifunctional theranostic agents for simultaneous diagnosis and therapy. We develop multifunctional nanoparticles based on NaGdF4:Yb/Er@NaGdF4 core–shell UCNPs, which are not only endowed with upconversion luminescence (UCL), magnetic resonance (MR) and X-ray computed tomography (CT) imaging ability, but also could be applied as nanocarriers for targeted drug delivery. We systematically investigate their upconversion luminescent, magnetic and X-ray attenuation properties. Importantly, for the first time, we report the controlled loading and delivery of a mixture of chemotherapeutic anticancer drugs, camptothecin (CPT) and doxorubicin (DOX), through UCNPs-based nanocarriers considering that the combined use of two or more drugs usually exhibits much better therapeutic efficacy than that of a single drug. By conjugating nanoparticles with folic acid (FA), which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted tri-modal UCL/MR/CT cell imaging and drug delivery with UCNPs. Our results suggest the as-prepared nanocomposites are highly versatile and could potentially be used for simultaneous imaging and therapeutic applications.

CAS / MDL: 59-30-3 143-19-1
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JOURNAL OF NANOPARTICLE RESEARCH · 2013 ·Vol. 15 ·期 12 ·1-14 · IF 2.175

New generation of β-cyclodextrin-chitosan nanoparticles encapsulated quantum dots loaded with anticancer drug for tumor-target drug delivery and imaging of cancer cells

Shu Chang,Li Ruixin,Guo Jin,Ding Li,Zhong Wenying

The objective of this study was to report the drug delivery system that can integrate the functional building blocks for optical pH-sensing, cancer cell imaging and controlled drug release into a single nanoparticle. The CD/SAHA-QDs-CS/FA nanoparticles were prepared by in-situ immobilization of ZnSe/ZnS quantum dots (QDs) in β-cyclodextrin (CD) and chitosan (CS) polymer loaded with suberoylanilide hydroxamic acid (SAHA). Synthetic CD/SAHA-QDs-CS/FA nanoparticles were approximately 100 nm in size and with blue fluorescence. The drug encapsulation efficiency of nanoparticles was 22.36 % and the encapsulated drug was released via a controlled release mechanism after a 9 h plateau was reached. The efficiency of the drug release in tumor microenvironments (pH 5.3 buffer solutions) was higher than that in physiological pH 7.4. In vitro cytotoxicity assay results showed that the blank nanoparticles had no cytotoxicity and therefore can be used as the fluorescence tracer, and the SAHA-encapsulated nanoparticles expressed an anticancer effect. Confocal microscopy and in vivo imaging studies showed that the developed nanoparticles had cytotoxicity in resistant cancer cells and preferentially accumulated in tumors. CD/SAHA-QDs-CS/FA nanoparticles with excellent long-term optical properties have great prospects for the development of targeting tracers and anti-tumor biomedical research.

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ANALYTICAL CHEMISTRY · 2013 · IF 5.695

Incorporation of Computed Tomography and Magnetic Resonance Imaging Function into NaYF4:Yb/Tm Upconversion Nanoparticles for in Vivo Trimodal Bioimaging

Ji-Wei Shen,Cheng-Xiong Yang,Lu-Xi Dong,Hao-Ran Sun,Kai Gao,Xiu-Ping Yan

Rational design and fabrication of multimodal imaging nanoprobes are of great significance for in vivo imaging. Here we report the fabrication of a multishell structured NaYF4:Yb/Tm@NaLuF4@NaYF4@NaGdF4 nanoprobe via a seed-mediated epitaxial growth strategy for upconversion luminescence (UCL), X-ray computed tomography (CT), and magnetic resonance (MR) trimodal imaging. Hexagonal phase NaYF4:Yb/Tm is used as the core to provide UCL, while the shell of NaLuF4 is epitaxially grown on the core not only to provide an optically inert layer for enhancing the UCL but also to serve as a contrast agent for CT. The outermost NaGdF4 shell is fabricated as a thin layer to give the high longitudinal relaxivity (r1) desired for MR imaging. The transition shell layer of NaYF4 not only provides an interface to facilitate the formation of NaGdF4 shell but also inhibits the energy transfer from inner upconversion activator to surface paramagnetic Gd3+ ions. The fabricated multishell structured nanoprobe shows intense near-infrared UCL, high r1 value of 3.76 mM–1 s–1, and in vitro CT contrast effect. The multishell structured nanoprobe offers great potential for in vivo UCL/CT/MR trimodal imaging. Further covalent bonding of folic acid makes the multishell structured nanoprobe promising for in vivo targeted UCL imaging of tumor-bearing mice.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomedical Physics & Engineering Express · 2015 ·Vol. 1 ·期 4 ·045009 · IF 0

Folate modified nanoparticles for targeted co-delivery chemotherapeutic drugs and imaging probes for ovarian cancer

Qiaoying Wang,Dan Wang,Danyang Li,Jian Lu,Qingrong Wei

Ovarian cancer has been the leading cause of death worldwide in gynecologic malignancy mainly due to the lack of ultrasensitive diagnosis approaches at its early stage and high cytotoxicity of anticancer drugs to normal cells. In an attempt to overcome the problems, a co-delivery system of folic acid (FA) modified nanoparticles were developed for early diagnosis and to maximize the therapeutic outcome. In the present study, we formulated a diblock copolymer of methoxy poly (ethylene glycol)-b-poly (-caprolactone)(mPEG-b-PCL) polymer micelles, and FA was further conjugated to endow micelles with active targeted capacity. Then paclitaxel (PTX) and superparamagnetic iron oxide (SPIO) were encapsulated in the core of micelles. The in vitro tumor cell targeting capability of FA-NP/SPIO/PTX and NP/ SPIO/PTX nanoparticles was assessed by confocal laser scanning microscopy (CLSM) with human ovarian cancer (SKOV3 cells) which overexpresses FA receptor. Quantitative analysis showed the amount of intracellular Fe in cells incubated with FA-NP/SPIO/PTX nanoparticles was about 13-fold higher than with NP/SPIO/PTX nanoparticles. The imaging contrast capability of FA-NP/SPIO/PTX nanoparticles as a sensitive MRI probe was evaluated by a 3 T clinical MR imaging scanner. The T2 -weighted imaging of cells incubated with targeting nanoparticles was found to have more sensitive imaging enhancement effect on the SKOV3 cells than non-targeting nanoparticles. Furthermore, the antitumor efficiency of targeting nanoparticles was approximately 5-fold higher than that of their counterparts, which further affirmed the feasibility of attaining the higher therapeutic efficacy of antitumor drugs while minimizing damage to healthy cells. The targeting nanoparticles exhibited the biphasic release characteristic in vitro. The results indicated that folate-modified nanoparticles could achieve high targeting specificity, high efficiency of delivery drug and excellent imaging enhancement. Therefore, the targeting nanoplatform has good prospects in non-invasively detecting early ovarian tumors, maximizing the therapeutic efficiency and real-time monitoring of therapeutic response, which can make it possible to lengthen patients' survival and ultimately achieve the goal of individualized medicine for ovarian cancer in the near future.

CAS / MDL: 59-30-3 27072-45-3
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Hydroquinone-Assisted Synthesis of Branched Au–Ag Nanoparticles with Polydopamine Coating as Highly Efficient Photothermal Agents

Jing Li,Wenjing Wang,Liang Zhao,Li Rong,Shijie Lan,Hongchen Sun,Hao Zhang,Bai Yang

Despite the success of galvanic replacement in preparing hollow nanostructures with diversified morphologies via the replacement reaction between sacrificial metal nanoparticles (NPs) seeds and less active metal ions, limited advances are made for producing branched alloy nanostructures. In this paper, we report an extended galvanic replacement for preparing branched Au–Ag NPs with Au-rich core and Ag branches using hydroquinone (HQ) as the reductant. In the presence of HQ, the preformed Ag seeds are replaceable by Au and, in turn, supply the growth of Ag branches. By altering the feed ratio of Ag seeds, HAuCl4, and HQ, the size and morphology of the NPs are tunable. Accordingly, the surface plasmon resonance absorption is tuned to near-infrared (NIR) region, making the branched NPs as potential materials in photothermal therapy. The branched NPs are further coated with polydopamine (PDA) shell via dopamine polymerization at room temperature. In comparison with bare NPs, PDA-coated branched Au–Ag (Au–Ag@PDA) NPs exhibit improved stability, biocompatibility, and photothermal performance. In vitro experiments indicate that the branched Au–Ag@PDA NPs are competitive agents for photothermal ablation of cancer cells.

CAS / MDL: 59-30-3
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Journal of Materials Chemistry B · 2015 ·Vol. 3 ·期 27 ·5478-5489 · IF 4.726

DOX-encapsulated intelligent PAA-g-PEG/PEG–Fa polymeric micelles for intensifying antitumor therapeutic effect via active-targeted tumor accumulation

Yong Sun,Yaning Wang,Yani Cui,Wen Zou,Yanfei Tan,Jie Liang,Yujiang Fan,Xingdong Zhang

Stimuli-responsive targeted polymeric micelles as drug delivery systems have recently attracted significant attention for the treatment of various cancers, which could improve delivery efficiency by tumor-specific recognition via active targeting strategies. In this research, DOX-incorporated bioreducible polymeric micelles based on PAA-g-PEG/PEG–Fa conjugated polymers were prepared and characterized as nanocarriers for promoting intracellular anti-tumor drug delivery efficiency via folate receptor-mediated endocytosis. The anti-proliferative activity on cancer cells, biodistribution, active-/passive-targeting efficiency, tumor growth inhibition efficiency, and biological toxicity were evaluated in vitro and in vivo. The MTT assay demonstrated that the DOX-encapsulated active-targeting PAA-g-PEG/PEG–Fa micelles had much greater growth inhibition effect against 4T1 and KB than passive-targeting micelles. These active-targeting micelles showed superior tumor accumulation and excellent tumor growth inhibition effect as revealed by the fluorescence optical imaging technique and tumor volume change investigation, as well as the survival study of the tumor-bearing Balb/c mice. Furthermore, the active targeting micelles greatly decreased the toxicity of DOX on the heart and other organs. These potential results encouraged us to further optimize the molecular structure to achieve more excellent targeted therapeutic effect.

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