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Polymer Chemistry · 2015 ·Vol. 6 ·期 15 ·2945-2954 · IF 5.52

Porphyrin-containing amphiphilic block copolymers for photodynamic therapy

Lei Xu,Lichao Liu,Feng Liu,Haibo Cai,Weian Zhang

Amphiphilic PNIPAM-b-PTPPC6MA block copolymers were first synthesized using porphyrin-containing monomers. The mono-hydroxylphenyl-triphenylporphyrin photosensitizer, TPP-OH, was modified into a porphyrin monomer, and it was further used to construct the amphiphilic PNIPAM-b-PTPPC6MA block copolymers using RAFT polymerization. PNIPAM-b-PTPPC6MA block copolymers can self-assemble into a plethora of morphologies ranging from spheres to vesicular aggregates and further to a single large vesicle. The PNIPAM-b-PTPPC6MA micelles exhibited a high singlet oxygen quantum yield. Moreover, confocal laser scanning microscopy (CLSM) and flow cytometry analysis confirmed that PNIPAM-b-PTPPC6MA micelles could effectively enhance the internalization rate in MCF-7 cells. According to the MTT assay, PNIPAM-b-PTPPC6MA micelles exhibited low dark toxicity and efficient PDT efficacy towards MCF-7 cells. Thus PNIPAM-b-PTPPC6MA block copolymers have the potential application for photodynamic therapy.

CAS / MDL: 298-93-1 47165-04-8
研究领域: 生物材料 · 肿瘤学 · 高分子化学
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CARBOHYDRATE POLYMERS · 2016 · IF 4.219

A novel porous aspirin-loaded (GO/CTS-HA)n nanocomposite films: Synthesis and multifunction for bone tissue engineering

Mingxiang Ji,Han Li,Hailin Guo,Anjian Xie,Shaohua Wang,Fangzhi Huang,Shikuo Li,Yuhua Shen,Jiacai He

A novel porous graphene oxide (GO)/chitosan (CTS)-hydroxyapatite (HA) nanocomposite film was successfully prepared for the first time by combining layer-by-layer (LBL) assembly technology with biomimetic mineralization method. The LBL technology was used to control the thickness of film as well as induce the biomimetic mineralization of biocompatible HA. The obtained (GO/CTS-HA) n film provided ideal platform for the proliferation of mouse mesenchymal stem cells (mMSCs). The pore size in the film is about 300   nm, and the porous architecture made the film have high aspirin loading efficiency. Also the accumulated loading dosage could be adjusted by the film thickness, and the sustained release of aspirin could ensure well anti-inflammatory effect. The above advantages may alleviate the pain of patients and give the better environment for bone regeneration. This multifunctional aspirin-loaded (GO/CTS-HA) n film provided an inspiration for the synthesis of novel porous inorganic/biomacromolecule nanocomposite films as the biocoatings applied in bone tissue engineering.

研究领域: 生物材料学 · 医学工程 · 细胞生物学
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International Journal of Nanomedicine · 2016 · IF 4.32

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

Yu Xin,Tie Liu,Chenlong Yang

We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.

CAS / MDL: 47165-04-8
研究领域: 药剂学 · 肿瘤学 · 生物医学工程
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LANGMUIR · 2016 · IF 3.993

Hydrophobic Carbon Nanodots with Rapid Cell Penetrability and Tunable Photoluminescence Behavior for in Vitro and in Vivo Imaging

Quan-Xing Mao,Shuang E,Jun-Mei Xia,Ru-Sheng Song,Yang Shu,Xu-Wei Chen,Jian-Hua Wang

Tunable fluorescent emission and applications in both in vitro and in vivo imaging of hydrophobic carbon nanodots (CNDs) with rapid penetration capability are reported. The hydrophobic CNDs are prepared via hydrothermal treatment of ionic liquid 1-ethyl-3-methylimidazolium bromide and exhibit excitation-dependent photoluminescence behavior along with a red-shift in the excitation/emission maxima with concentration. The quantum yields of the as-prepared CNDs are in the range of 2.5–4.8% at an excitation wavelength of 300–600 nm. The rapid penetration behavior (within 1 min) of CNDs into the cell membrane significantly reduces the sample treatment time and avoids potential fluorescence quenching induced by the interaction between CNDs and samples. A co-location study reveals that the hydrophobic CNDs are distributed mainly in the lysosome. The potentials of the hydrophobic CNDs as fluorescent probe in in vitro and in vivo imaging are well demonstrated by the labeling of HeLa cells, MCF-7 cells, A549 cells, and Kunming mice.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 细胞生物学 · 成像科学
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Biomaterials Science · 2016 ·Vol. 5 ·期 2 ·274-284 · IF 3.614

Intracellular GSH-activated galactoside photosensitizers for targeted photodynamic therapy and chemotherapy

Chaochao Wang,Lichao Liu,Hongliang Cao,Weian Zhang

Ligand-targeted cancer therapeutics has been developed to minimize non-specific cytotoxicity via ligand–drug conjugates during the past few decades. We present here the design and synthesis of a GSH-activated amphiphilic photosensitizer conjugated with galactose (TPP-S-S-Gal) for targeted photodynamic therapy. Furthermore, the galactoside photosensitizer as supramolecular amphiphiles can self-assemble into micelles, which can be applied in integrative cancer treatment with chemotherapy drugs such as camptothecin (CPT) encapsulated in the hydrophobic core of micelles. Upon reaction with free thiol GSH that is relatively abundant in tumor cells, disulfide bond cleavage occurs as well as the active photosensitizer TPP and chemotherapy drug CPT release, which can cause cell apoptosis. The in vitro biological assessment of TPP-S-S-Gal micelles against the A549 cell line was evaluated by MTT assay, flow cytometry and confocal scanning laser microscopy, respectively. According to the MTT assay, TPP-S-S-Gal micelles exhibited low dark toxicity and efficient integrative efficacy of PDT and chemotherapy towards A549 cells after light irradiation.

研究领域: 药理学 · 肿瘤学 · 生物化学
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Triple Stimuli-Responsive Magnetic Hollow Porous Carbon-Based Nanodrug Delivery System for Magnetic Resonance Imaging-Guided Synergistic Photothermal/Chemotherapy of Cancer

Fan Wu,Ming Zhang,Hanwen Lu,Dong Liang,Yaliang Huang,Yonghong Xia,Yuqing Hu,Shengqiang Hu,Jianxiu Wang,Xinyao Yi,Jun Zhang

The premature leakage of anticancer drugs during blood circulation may the damage immune system, normal cells, and tissues. Constructing targeted nanocarriers with pH, glutathione, and NIR triple-responsive property can effectively avoid the leakage of anticancer drugs before they arrive at the targeted site. In this paper, magnetic hollow porous carbon nanoparticles (MHPCNs) were successfully fabricated as nanocarrier. Poly(γ-glutamic acid) was used to cap the pores of MHPCNs. The photothermal conversion property of carbon and iron oxide (Fe3O4) nanomaterials was utilized to perform photothermal therapy to overcome multidrug-resistance produced by chemotherapy. The biodistribution of nanoparticles was investigated by magnetic resonance imaging. Experiments in vivo confirm the efficient accumulations of nanoparticles at tumor sites. Meanwhile, tumor growth was effectively inhibited via synergistic photothermal/chemotherapy with minimal side effects.

研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 磁共振成像 · 光热治疗
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International Journal of Nanomedicine · 2018 · IF 4.37

Preparation of ginsenoside compound-K mixed micelles with improved retention and antitumor efficacy

Xin Jin,Qing Yang,Ning Cai

Introduction Ginsenoside compound K (CK) has effects on cell-cycle regulation, tumor growth inhibition, and apoptosis induction. However, it has limited applications in clinical settings because of its low solubility and poor absorption. Methods To overcome these limitations, we aimed to develop a mixed micellar system composed of phosphatidylcholine (PC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE PEG 2000; DP). CK encapsulated in PC/DP mixed micelles had enhanced solubility, permeability, and retention effects. Results Compared to free CK, the CK PC/DP micellar system exhibited improved anticancer effects in vitro, including cell-cycle arrest, apoptosis, and anti-invasion in human lung carcinoma A549 cells. The significant proapoptotic effect was reflected by increased chromosomal condensation, annexin V/propidium iodide staining, and related protein expression. In vitro cellular uptake and optical mouse imaging in vivo suggested that the improved antitumor effect was caused primarily by enhanced uptake and tumor targeting. Furthermore, an in vivo antitumor efficacy study indicated that the CK mixed micelles significantly inhibited tumor growth, thereby decreasing tumor volume at the end of the experiment as compared with that in the control mice. Histological analysis confirmed the antitumor effect with low toxicity. Conclusion The PC/DP micellar system was an effective drug delivery system for CK in tumor therapy.

CAS / MDL: 38215-36-0 47165-04-8
研究领域: 药学 · 肿瘤学 · 药物递送系统 · 药理学
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BIOSENSORS & BIOELECTRONICS · 2015 · IF 6.409

Sensitive detection for coralyne and mercury ions based on homo-A/T DNA by exonuclease signal amplification

Hailiang Huang,Shuo Shi,Xuyue Zheng,Tianming Yao

Based on specific homo-A/T DNA binding properties, a strategy for coralyne and mercury ions detection was realised by exonuclease-aided signal amplification . Coralyne could specifically bind homo-A DNA and protect it from the hydrolysis of exonuclease I. The coralyne-protected DNA was subsequently used as a trigger strand to hydrolyze DNA2 in exonuclease-aided signal amplification process. Thiazole orange was used to quantify the remainder DNA2. Under the optimal condition, the fluorescence intensity was linearly proportional to the concentration of coralyne in the range of 0.2–100   nM with a limit of detection (LOD) of 0.31   nM, which presented the lowest LOD for coralyne among all reported. With homo-T and Hg 2+ taking the place of homo-A DNA and coralyne, respectively, the system could also be used for Hg 2+ detection. The experiments in real samples also showed good results. This method was label-free, low-cost, easy-operating and highly repeatable for the detection of coralyne and mercury ions. It could also be extended to detect various analytes, such as other metal ions, proteins and small molecules by using appropriate aptamers.

研究领域: 分析化学 · 生物化学 · 环境科学
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Nanoscale Research Letters · 2018 ·Vol. 13 ·期 1 ·1-10 · IF 3.125

Artesunate-Loaded and Near-Infrared Dye-Conjugated Albumin Nanoparticles as High-Efficiency Tumor-Targeted Photo-Chemo Theranostic Agent

Yang Hainan,Liu Zaijia,Li Xufeng,Zhang Zhenfeng,Chen Deji,Lian Hui

Herein, a tumor-targeted multifunctional theranostic agent was synthetized using a facile method, combining four clinically approved materials: artesunate (Arte), human serum albumin (HSA), folic acid (FA), and indocyanine green (ICG). The obtained nanocomposites (FA-IHA NPs) showed an excellent photo- and physiological stability. The ICG in the FA-IHA NPs was used not only for near infrared (NIR) fluorescence imaging, but also for photothermal and photodynamic (PTT-PDT) therapy under a single NIR irradiation. In addition, the NIR irradiation (808 nm, 1 W/cm 2 ) could trigger Arte release that showed enhanced chemotherapeutic effect. Through fluorescence imaging, the cell uptake and tumor accumulation of FA-IHA NPs were observed in vitro and in vivo, analyzed by confocal microscopy and NIR fluorescence imaging in tumor xenograft mice. Based on the diagnostic results, FA-IHA NPs at 24 h post injection and combined with NIR irradiation (808 nm, 1 W/cm 2 ) could efficiently suppress tumor growth through a photo-chemo combination therapy, with no tumor recurrence in vitro and in vivo. The obtained results suggested that FA-IHA NPs are promising photo-chemo theranostic agents for future clinical translation.

CAS / MDL: 25126-32-3 47165-04-8
研究领域: 纳米医学 · 肿瘤学 · 药剂学 · 生物材料
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ACS Omega · 2018 · IF 0

Fabrication of Bis-Quaternary Ammonium Salt as an Efficient Bactericidal Weapon Against Escherichia coli and Staphylococcus aureus

Zhiyong Song,Huajuan Wang,Yang Wu,Jiangjiang Gu,Shuojun Li,Heyou Han

Combating bacterial pathogens has become a global concern, especially the emergence of drug-resistant bacteria have made conventional antibiotics lose their efficiency. This grim situation suggests the necessity to explore novel antibacterial agents with favorable safety and strong antibacterial activity. Here, we took the advantage of quaternary ammonium compounds and synthesized a long-chain high-molecular organic bis-quaternary ammonium salt (BQAS) with a broad-spectrum bactericidal activity through a facile one-pot reaction. The bactericidal effect of BQAS was evaluated by two bacterial human pathogens: Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), which are the major cause of diarrheal infections in children and adults. Our experimental results indicate that the bactericidal activity of BQAS is linked to the strong contact between the positively charged quaternary ammonium groups and the bacterial cells, thus leading to a temporary and locally high concentration of reactive oxygen species, which subsequently triggers oxidative stress and membrane damage in the bacteria. This mechanism was further confirmed by several assays, such as the membrane permeabilization assay, fluorescent-based cell live/dead test, scanning electron microscopy, transmission electron microscopy, together with the lactate dehydrogenase release assay, which all indicated that BQAS induced damage to the cytoplasmic membrane and the leakage of intracellular fluid containing essential molecules. The excellent bactericidal activity of BQAS suggests its great application potential as a promising candidate against the rapid emergence of drug-resistant bacterial pathogens.

研究领域: 微生物学 · 药物化学 · 生物医学工程
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Journal of Materials Chemistry B · 2018 ·Vol. 6 ·期 48 ·8078-8084 · IF 4.776

Lipid bilayer modified gold nanorod@mesoporous silica nanoparticles for controlled drug delivery triggered by near-infrared light

Xinyu Cui,Wenlong Cheng,Xiaojun Han

Integration of various theranostic modalities into one nanoplatform for combined treatment of tumor is highly desirable in the field of biomedicine. However, it is still challenging to engineer such a platform with good biocompatibility, multifunctionality, and response to external stimuli. Herein, biocompatible lipid bilayer modified mesoporous silica coated gold nanorods (AuNRs) nanocomposites were developed. The heat from near-infrared (NIR)-stimulated AuNR cores could improve the permeability of the lipid bilayer, thereby leading to drug release. The in vitro results exhibited the DOX loaded nanocomposites to have high treatment efficiency in HeLa cells upon NIR irradiation. They may find potential in cancer treatment.

CAS / MDL: 298-93-1 47165-04-8
研究领域: 生物医学 · 纳米医学 · 肿瘤学
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CARBOHYDRATE POLYMERS · 2018 · IF 5.158

A photo-controlled hyaluronan-based drug delivery nanosystem for cancer therapy

Feifei Sun,Peng Zhang,Yinyin Liu,Chunbo Lu,Yuanhao Qiu,Haibo Mu,Jinyou Duan

In this paper, a novel photo-controlled drug-loaded nanomicelles were self-assembled by the amphiphile of hyaluronan- o -nitrobenzyl-stearyl chain (HA-NB-SC) with doxorubicin (DOX) encapsulated within the hydrophobic core. DOX-loaded HA-NB-SC nanomicelles are ∼139 nm in diameter. CD44-overexpressed HeLa cells can easily take up HA-NB-SC micelles through recognition of HA moiety. DOX-loaded HA-NB-SC nanomicelles could be disassembled upon UV light (365 nm) and consequently, release DOX at desired pathological sites. Furtherly, nitrosobenzaldehyde derivative, photo-induced products of HA-NB-SC and DOX could inhibit the proliferation of HeLa cells together. This strategy may shed some light on delivery of hydrophobic anti-cancer drugs in a controlled manner.

研究领域: 药学 · 生物医学工程 · 肿瘤学
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