Materials Science & Engineering C-Materials for Biological Applications
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2016
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IF 3.42
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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Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Lei Li,Guohua Jiang,Weijiang Yu,Depeng Liu,Hua Chen,Yongkun Liu,Qin Huang,Zaizai Tong,Juming Yao,Xiangdong Kong
Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro . In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo . After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
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IF 3.887
Jing Cao,Yahui Zhang,Yukun Wu,Jing Wu,Wei Wang,Qiang Wu,Zhi Yuan
It has been shown that multivalent ligands could significantly enhance the binding avidity compared with the monovalent ones; therefore, once incorporated into nanoparticles, they promote superior targeting ability without increasing the ligand density. Although ligand valency and density play a key role on the targeting ability of corresponding nanoparticles, these facotrs remain largely unexplored and detailed studies are lacking. Herein, a series of multivalent ligands with certain valencies (FA n , n indicates the valency of ligand: n = 3, 5, 7) has been conveniently synthesized by conjugating different copies of folate ligands with poly(acrylic acid) (PAA). Negatively charged chitosan nanoparticles (CTS-SA NPs) have been utilized as proper multivalent platforms because they can strongly suppress non-specific protein adsorption and cellular uptake without interfering with the targeting ability of multivalent ligands. Subsequently, the structure of CTS-SA NPs has been modified using different amounts of FA n to form multivalent nanoparticles (FA n -CTS-SA NPs) with various valencies and densities. A series of specific investigations of them suggested that the cellular uptake of multivalent nanoparticles has largely varied with the ligand valency variation even at similar ligand densities; and also largely varied with ligand density variation even at the same ligand valencies. The intermediate valency and density values determined in the current study ( ie., 5 and 2.4 wt%, respectively) have provided the best cellular uptake, facilitating superior targeting ability at relatively low ligand valency and density. Unexpectedly, no conspicuous difference has been observed during endocytotic inhibition assays with single inhibitors, which may be attributed to the synergetic endocytotic mechanism with multiple pathways of multivalent nanoparticles. The optimal multivalent nanoparticles have also exhibited excellent biocompatibility, long-term stability in vitro and enhanced circulation time in vivo , thus demonstrating their potential for targeted drug delivery.
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Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
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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Oncotarget
·
2016
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IF 5.008
Tao Liu,Xidong Wu,Yigang Wang,Tao Zhang,Ting Wu,Fang Liu,Wansong Wang,Gang Jiang,Minqiang Xie
The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
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IF 3.994
Kang Chen,Qing Chen,Kuanglei Wang,Jia Zhu,Weinan Li,Wenpan Li,Lipeng Qiu,Guannan Guan,Mingxi Qiao,Xiuli Zhao,Haiyang Hu,Dawei Chen
The present report describes the synthesis of a hydroxyl terminal PAMAM dendrimer (PAMAM-OH) derivative (PAMSPF). The hydroxyls of PAMAM-OH were attached to S-Methyl- l -cysteine (SMLC) via an acid-labile ester bond, named as β-thiopropionate bond, followed by modification with folic acid (FA) through a polyethylene glycol (PEG) linker. The degrees of attachment of SMLC and FA to the PAMAM-OH backbone were 83.9% and 12.8%, respectively. PAMSPF could condense DNA to form spherical nanoparticles with particle sizes of ∼200 nm and remain stable in the presence of heparin and nuclease . The β-thiopropionate bond in PAMSPF was hydrolyzed completely and the DNA release rate was 95.8 ± 3.3% after incubation under mildly acidic conditions at 37 °C for 3 h. PAMSPF/DNA was less cytotoxic to KB and HepG2 cells and exhibited a higher gene transfection efficiency than native PAMAM/DNA. The uptake assays showed that PAMSPF/DNA entered KB cells within 0.5 h through folate receptor-mediated endocytosis and escaped from endosomes within 2 h. In addition, PAMSPF/DNA displayed long circulation time along with excellent targeting of tumor sites in vivo. These findings demonstrate that PAMSPF is an excellent carrier for safe and effective gene delivery.
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ANALYST
·
2016
·Vol. 141
·期 15
·4713-4718
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IF 4.033
Wenyu Gao,Qing Zheng,Zongxu Shen,Hao Wu,Yuehui Ma,Weijun Guan,Songmei Wu,Yu Yu,Kejian Ding
A highly sensitive and selective tumor cell sensor based on partially oxidized graphene (POG) and folate acid (FA) composite was constructed. The POG was prepared through a modified Hummers method and characterized by means of Raman spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammetry, atomic force microscopy and transmission electron microscopy. The as-prepared POG exhibited the advantages of high electrochemical activity and a good capacity of linking amine derivatives. Using a facile one step reaction, the FA-modified POG was endowed with a more sensitive response to folate-expressing tumor cells than those sensors constructed by the two-step reaction, as well as high selectivity, good reproducibility and long-term stability.
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Journal of Materials Chemistry B
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2017
·Vol. 5
·期 18
·3300-3314
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IF 4.543
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.
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Biomed Research International
·
2016
·
IF 2.134
Yue Hu,Yong Wang,Jianshuai Jiang,Baosan Han,Shengmin Zhang,Keshi Li,ShuXiong Ge,Yahui Liu
A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor.
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REACTIVE & FUNCTIONAL POLYMERS
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2017
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IF 3.151
Chaoyue Hao,Jianping Gao,Yongli Wu,Xiaoxue Wang,Ruiru Zhao,Shunkang Mei,Jiangbing Yang,Xiangang Zhai,Haixia Qiu
Folic acid (FA) supramolecular gel was prepared in a mixture solvent of N -methylpyrrolidone (NMP)/H 2 O at a 1/1 volume ratio by using FA as gelator with a concentration of 0.4% (w/v). In the mixture solvent, NMP was first of time used as a good solvent to tune the solvent properties in order to be able to induce formation of FA supramolecular gel. The folic acid-gelatin (FA-GA) hybrid gels were synthesized by adding different amount of gelatin (GA) into FA gelator. The gelation temperature (T Gel ) of the FA-GA hybrid gel is 30 °C which is much higher than that of FA gel (10 °C). The gel to sol transition temperature (T GS ) is about 58 °C, which demonstrates that the hybrid gel has good stability at room temperature . The FT-IR and UV–vis spectra of FA-GA hybrid gel indicate that GA involves in the self-assembly process of FA via hydrogen bonding and π-π interactions with FA molecules. Owing to the π-π interaction happened between FA and GA molecules the fluorescence intensity of FA-GA gel is four times as high as that of FA gel. SEM images shows that the hybrid gel has a helical-fiber network structure which would enhance the gel strength to a great extent. Good stability, large specific surface and porosity in three-dimensional network structure of the FA-GA hybrid gel make it a highly promising adsorbent for dye adsorption. The FA-GA hybrid gel is able to absorb 63.5% of Congo red (CR), 68% of methyl blue (MB) and 44% of methyl orange (MO) respectively from their solutions.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
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IF 3.887
Zhili Deng,Menghuan Tang,Li Zhao,Yijuan Long,Zuhuang Wen,Yuan Cheng,Huzhi Zheng
A novel targeting drug delivery system for cancer therapy based on H + -triggered bubble-generating nanosystems (BGNSs) was engineered. First, hollow mesoporous silica nanoparticles (HMSNs) were used to load doxorubicin (DOX). Then, the obtained drug-loaded HMSNs were treated with NaHCO 3 to prepare the BGNSs. The BGNSs were coated with polydopamine (pDA), and finally, folic acids (FA) were anchored on the nanosystems to obtain the desired nanoscale drug delivery system ( [email protected] ). [email protected] was effectively internalized by cancer cells through folate receptor-mediated endocytosis and generated CO 2 bubbles under the acidic environment of the lysosomes, thus enhancing lysosomal membrane permeability (LMP) to release caspase-3 into the cytoplasm, resulting in cancer cell death via an apoptosis-like pathway. Notably, we demonstrated that the [email protected] exhibited a significant simultaneous synergetic cytotoxicity against MCF-7 cells and remarkably overcame the multidrug resistance (MDR) of MCF-7/ADR cells. Moreover, compared to free DOX and a nanosystem without FA modification (BGNSs), the [email protected] induced relatively minor side effects in the MCF-10A cells. Therefore, the results showed that [email protected] , as a targeted drug delivery system, have a good probability of overcoming the MDR of tumor cells with minor side effects on normal cells.
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BIOMATERIALS
·
2016
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IF 8.387
Qiuming Liu,Liwen Song,Shuai Chen,Jingyi Gao,Peiyu Zhao,Jianzhong Du
Improving the relaxivity of magnetic resonance imaging (MRI) contrast agents is an important challenge for cancer theranostics. Herein we report the design, synthesis, characterization, theoretical analysis and in vivo tests of a superparamagnetic polymersome as a new MRI contrast agent with extremely high T 2 relaxivity (611.6 mM −1 s −1 ). First, a noncytotoxic cancer-targeting polymersome is synthesized based on a biodegradable diblock copolymer , folic acid-poly( l -glutamic acid)- block -poly( ε -caprolactone) [FA-PGA- b -PCL]. Then, ultra-small superparamagnetic iron oxide nanoparticles (SPIONs) are in situ generated in the hydrophilic PGA coronas of polymersomes to afford magnetic polymersomes. The in vivo MRI assay revealed prominent negative contrast enhancement of magnetic polymersomes at a very low Fe dose of 0.011 mmol/kg. Moreover, this cancer-targeting magnetic polymersome can effectively encapsulate and deliver anticancer drug to inhibit the tumor growth, demonstrating promising theranostic applications in biomedicine .
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