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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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RSC Advances · 2015 ·Vol. 5 ·期 29 ·22343-22349 · IF 3.84

Controllable and mass fabrication of highly luminescent N-doped carbon dots for bioimaging applications

Zhao Chen,Xiaochi Wang,Hua Li,Chao Li,Qinghua Lu,Guang Yang,Jiangang Long,Lingjie Meng

A facile but effective bottom-up method for the mass preparation of N-doped carbon dots (N–C-dots) was developed by the direct heating of a solid mixture of folic acid (FA) and sodium citrate (SC) for several minutes at 300 °C. The nitrogen content of the resulting N–C-dots could be easily and precisely tuned from 0% to 14% by adjusting the SC to FA mass ratio. Uniform N–C-dots with honeycomb-like ordered structures were obtained, with sizes ranging from 1 to 3 nm in diameter. The N-doping content affected not only the emission quantum yield but also the emission wavelength. The N–C-dots emitted strong blue-green fluorescence based on the excitation wavelength and N-doping content. Because of their excellent water solubility, low toxicity, powerful fluorescence, and high resistance to photobleaching, the N–C-dots can enter various cells and serve as ideal candidates for multicolour cell imaging.

CAS / MDL: 59-30-3 68-04-2
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RSC Advances · 2016 ·Vol. 6 ·期 46 ·40312-40322 · IF 3.289

Folic acid targeted pH-responsive amphiphilic polymer nanoparticles conjugated with near infrared fluorescence probe for imaging-guided drug delivery

Liyi Fu,Le Liu,Zheng Ruan,Houbing Zhang,Lifeng Yan

A novel folic acid targeted pH-responsive amphiphilic polymer conjugated with near infrared (NIR) probe has been synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(N-tert-butoxycarbonylamino)ethyl methacrylate (BEMA) and oligo(ethylene glycol)methacrylate (OEGMA), ring-opening polymerization of N-carboxy anhydride (NCA) and click reaction. After assembling to micelles, the polymeric nanoparticles has pH-responsive properties for delivery encapsulated drug into the tumor cell via a rapid process of expansion and subsequent disassembly. Folic acid linked to the amino groups on the branched chains would promote the endocytosis of the polymeric nanoparticles by the cells leading the improvement of the effect of doxorubicin (DOX). In vitro experiments on both MCF7 and HepG2 cells revealed the as-prepared polymer might be a potential candidate for future theranosic against cancer.

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Nanoscale · 2016 ·Vol. 8 ·期 18 ·9798-9804 · IF 7.76

One-step synthesis of amino-functionalized ultrasmall near infrared-emitting persistent luminescent nanoparticles for in vitro and in vivo bioimaging

Junpeng Shi,Xia Sun,Jianfei Zhu,Jinlei Li,Hongwu Zhang

Near infrared (NIR)-emitting persistent luminescent nanoparticles (NPLNPs) have attracted much attention in bioimaging because they can provide long-term in vivo imaging with a high signal-to-noise ratio (SNR). However, conventional NPLNPs with large particle sizes that lack modifiable surface groups suffer from many serious limitations in bioimaging. Herein, we report a one-step synthesis of amino-functionalized ZnGa2O4:Cr,Eu nanoparticles (ZGO) that have an ultrasmall size, where ethylenediamine served as the reactant to fabricate the ZGO as well as the surfactant ligand to control the nanocrystal size and form surface amino groups. The ZGO exhibited a narrow particle size distribution, a bright NIR emission and a long afterglow luminescence. In addition, due to the excellent conjugation ability of the surface amino groups, the ZGO can be easily conjugated with many bio-functional molecules, which has been successfully utilized to realize in vitro and in vivo imaging. More importantly, the ZGO achieved re-excitation imaging using 650 nm and 808 nm NIR light in situ, which is advantageous for long-term and higher SNR bioimaging.

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Nanoscale · 2016 ·Vol. 8 ·期 18 ·9837-9841 · IF 7.76

Fluorescent non-conjugated polymer dots for targeted cell imaging

Bin Sun,Bin Zhao,Dandan Wang,Yibo Wang,Qi Tang,Shoujun Zhu,Bai Yang,Hongchen Sun

Through the chemical crosslinking of the sub-fluorophore, linear non-conjugated polymers can possess strong photoluminescence (PL), which is a very important fluorescence behavior and the non-conjugated polymer dots (PDs) are efficient bio-fluorophores for bio-based applications. Herein, the new type of non-conjugated polyethyleneimine (PEI) PDs was further modified by targeting molecules (folic acid) for a new generation of bio-fluorophores. The free folic acid can quench the PL of PDs by energy transfer, while the conjugated folic acid@PDs (FA@PDs) can still maintain their PL properties to a certain degree. The FA@PDs also possess lower toxicity compared with free PDs, which is possibly due to blocking of the amino groups. Moreover, we investigated the targeted bioimaging applications of the FA@PDs, which gave a very important direction for application of these types of materials.

CAS / MDL: 9002-98-6 59-30-3
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RSC Advances · 2016 ·Vol. 6 ·期 42 ·35658-35667 · IF 3.289

Folate-conjugated dually responsive micelles for targeted anticancer drug delivery

Lingling Zhao,Yajuan Zhang,Jia Shao,Hongze Liang,Haining Na,Jin Zhu

Phenylboronic acid and folate grafted chitosan hydrochloride (FHCSPBA) was synthesized and confirmed by FTIR and 1H NMR. Glucose and pH dually responsive micelles were obtained through self-assembly of the amphiphilic polymers. The prepared FHCSPBA micelles displayed good biocompatibility and sustained drug release of the model drug doxorubicin hydrochloride (DOX). The cumulative drug release from the polymeric micelles showed obvious pH and glucose dependence and was accelerated by slightly decreasing the medium pH or increasing the glucose concentration. In vitro antitumor efficiency was evaluated by incubating the DOX loaded micelles with 4T1 breast cancer cells, and the results showed that folate-targeted micelles had higher antitumor activity than the non-targeted ones. Cellular uptake demonstrated by confocal microscopy indicated that free DOX was internalized in the nuclei of 4T1 cells, while the DOX loaded micelles were internalized in the cytoplasm. The cellular uptake of the micelles was enhanced by folate, with stronger fluorescence intensity in the cytoplasm, due to active FR-mediated endocytosis. These folate-conjugated glucose and pH dually responsive micelles may be a potential antitumor drug delivery system for cancer chemotherapy.

CAS / MDL: 59-30-3
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NEW JOURNAL OF CHEMISTRY · 2017 ·Vol. 41 ·期 10 ·3766-3772 · IF 3.269

Synthesis and properties enhancement of metal nanoclusters templated on a biological molecule/ionic liquids complex

Wei Wang,Xiaolun Peng,Huayu Xiong,Wei Wen,Ting Bao,Xiuhua Zhang,Shengfu Wang

In this study, two biological template molecules and two common short-chain imidazolium ionic liquids with amphipathy were selected to synthesize four different types of metal nanoclusters (MNCs), which were templated on a biological molecule/imidazolium ionic liquids (ILs) complex with properties enhancement. The fluorescence intensity and stability of the MNCs were improved in different degrees via this simple and fast protocol. The fluorescence intensity of AgNCs was significantly enhanced primarily due to aggregation-induced emission (AIE), and it was attributed to the shrinking size and donation of delocalized electrons for other MNCs. Different template molecule must match with appropriate ILs to form a steady complex that stabilizes the MNCs. The stability of the MNCs was improved, especially for AuNCs, because biological molecule/imidazolium ILs complex was found to be an effective barrier in protecting the MNCs from quenching interactions. Compared to conventional cationic surfactant (sodium dodecyl sulfate, SDS), these imidazolium ILs exhibited superior properties enhancement of the nanomaterials. MNCs with excellent properties could be applied in bioanalysis, especially in fluorescence imaging in vitro, because of their undisturbed and durable optical signal.

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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 18 ·3300-3314 · IF 4.543

Phycocyanin-based nanocarrier as a new nanoplatform for efficient overcoming of cancer drug resistance

Yanyu Huang,Lizhen He,Zhenhuan Song,Leung Chan,Jintao He,Wei Huang,Binwei Zhou,Tianfeng Chen

Resistance to chemotherapy remains the primary obstacle for the successful treatment of cancers. Nanotechnology-based studies have developed many smart nanomedicines and efficient strategies to overcome multidrug resistance (MDR), which have brought new horizons to cancer therapy. Among them, protein-based nanomedicine represents an appealing drug delivery platform to realize safe and superior therapeutic effects due to its paramount biocompatibility with minimized toxicity. Herein we describe the rational design and construction of a novel protein-based nanocarrier using the naturally-occurring protein phycocyanin (PC) as the base material, to achieve safe and tumor-specific drug delivery. This cancer-targeting nanosystem (FA-PCNP@DOX) with bio-responsive properties exhibits positive targeting accumulation in resistant cancer cells and overcomes drug efflux by enhancing cellular uptake and retention time. Specifically, FA-PCNP@DOX inhibits the function of pumping proteins of the ABC family and triggers ROS-mediated apoptotic signaling pathways, thereby attaining highly efficient anticancer efficacy and overcoming drug resistance. Pharmaceutical studies demonstrate that FA-PCNP@DOX overwhelms DOX by sustained release in the blood, which verifies its prolonged circulation in vivo. Moreover, FA-PCNP@DOX efficiently accumulates in tumors and strengthens the tumor inhibitory effect of DOX by enhanced tumoral penetration. Importantly, FA-PCNP@DOX effectively reduces the hepatic, pulmonary, renal and cardiac toxicity caused by DOX. Therefore, as a new nanocarrier, this novel nanosystem could be further exploited as a safe and versatile nanoplatform for next-generation cancer therapy.

CAS / MDL: 25952-53-8 59-30-3
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Preparation of poly(lactic-co-glycolic acid) and chitosan composite nanocarriers via electrostatic self assembly for oral delivery of insulin

Bin Xu,Guohua Jiang,Weijiang Yu,Depeng Liu,Yongkun Liu,Xiangdong Kong,Juming Yao

To improve insulin bioavailability and overcome multiple barriers for oral delivery of insulin, the composite nanocarriers (PLGA/FA-CS) prepared from poly(lactide- co -glycoside) (PLGA) and folic acid modified chitosan (FA-CS) were fabricated via electrostatic self-assembly method. The resultant composite nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that the as-prepared composite nanocarriers may be a promising drug delivery system for oral administration of insulin and other biomacromolecules.

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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Photoresponsive hollow molecularly imprinted polymer for trace triamterene in biological samples

Cheng-Bin Gong,Yu-Bo Wei,Lan-Tao Liu,An-Xun Zheng,Yue-Hong Yang,Cheuk-fai Chow,Qian Tang

This paper reports a photoresponsive hollow molecularly imprinted polymer for the determination of trace triamterene in biological sample. The photoresponsive hollow molecularly imprinted polymer was prepared on sacrificial silica microspheres via surface imprinting technique through atom transfer radical polymerization using a novel water-soluble azobenzene derivative, 4-[(4-methacryloyloxy)phenylazo]-3,5-dimethyl benzenesulfonic acid, as the functional monomer, and the sacrificial silica core was subsequently removed using HF etching method with 1.25   vol.% HF ethanolic solution. The morphologies and properties of the photoresponsive hollow molecularly imprinted polymer were further characterized and compared systematically with the corresponding photoresponsive surface molecularly imprinted polymer. Compared with surface imprinted polymer, the hollow material displayed higher binding capacity, better recognition ability, faster mass-transfer rate, and larger isomerization rate constants toward triamterene. The static binding properties of the imprinted materials were investigated under three irradiation conditions. The photoresponsive hollow molecularly imprinted polymer showed better specificity toward triamterene than its structural analogues (folic acid and caffeine) as examined by UV–vis and HPLC. The photoresponsive hollow molecularly imprinted polymer was utilized for the determination of trace triamterene in biological samples (human urine and serum) with advantages of simple sample pre-treatment, good recovery and good sensitivity.

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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

Gated magnetic mesoporous silica nanoparticles for intracellular enzyme-triggered drug delivery

Na An,Huiming Lin,Chunyu Yang,Ting Zhang,Ruihan Tong,Yuhua Chen,Fengyu Qu

The targeting drug release is significant to the anticancer treatment. In this context, the redox-responsive drug delivery has attracted most attention owing to the intracellular reductive environment, such as the high concentration of glutathione reductase in many cancer cells. Herein, a glutathione sensitive drug delivery nanoplatform was constructed by using core-shell mesoporous silica nanocomposite (Fe 3 O 4 @mSiO 2 ) as carrier. By a simple silane coupling reaction, the glutathione cleavable diselenide linker has been prepared and grafted on to Fe 3 O 4 @mSiO 2 to insure the encapsulation of anticancer drug doxorubicin. The detail release kinetics studies reveal the glutathione triggered drug release, which could be further adjusted by varying the amount of diselenide linker. To improve the tumor-targeting, folic acid was grafted. The cellular uptake and drug release investigation was carried out using HeLa (cervical cancer cell line) as the model cancer cell and L02 and HUVEC (human hepatic cell line and human umbilical vein endothelial cells, non-cancerous cell lines) as control, indicating the enhanced cytotoxicity toward HeLa cells that benefits from the fast endocytosis and enhanced cellular drug release owing to their overexpressing folic acid receptors and high concentration of glutathione. Associating with the magnetic targeting, these novel nanomaterials are expected to be promising in the potential application of tumor-targeting therapy.

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