PHARMACEUTICAL CHEMISTRY JOURNAL
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2024
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IF 0.8
Pan Boyuan,Fu Linna,Du Heng,Liu Guangbin,Duan Bingchao,Lu Kui
RAD51 is a core factor for homologous recombination to repair DNA double-strand breaks and overexpressed in breast cancer cells. Truncated peptide BRC4 (1523-1537) was obtained by computer simulation which had the highest binding free energy targeting RAD51. To enhance the binding affinity to the target protein, six nicotinic acid derivatives were modified at the N -terminal of BRC4 (1523-1537) by Fmoc solid-state synthesis to obtain nicotinamide-modified peptides. The interaction of RAD51 (181-200) with BRC4 (1523-1537) and nicotinamide-modified peptides was verified by circular dichroism (CD) spectroscopy and fluorescence spectroscopy. In conclusion, modifying small molecule pharmacophores can improve binding ability. According to spectral results, 2-chloro-5-fluoronicotinic acid modified BRC4 (1523-1537) has the most significant influence on the secondary structure of RAD51 (181-200); binding constant is 1.1×10 4 L·mol -1 . Cell experiments showed that BRC4 (1523-1537) modified with nicotinic acid N-oxide had the best inhibitory effect on the proliferation of MDA-MB-231 cells.
研究领域:
生物化学
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癌症研究
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药物设计
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yutong Wang,Yiming Huo,Chunyuan Zhao,Heng Liu,Yurou Shao,Chenqi Zhu,Lan An,Xiao Chen,Zhipeng Chen
Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.
研究领域:
医学
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Coatings
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2023
·Vol. 13
·期 10
·1711
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IF 3.4
Zhimin Cao,Qian Guo
Long-term immersion in seawater easily causes surface fouling and affects the marine aquaculture industry. The commonly used method is to apply copper-based coatings on surfaces, however, the release of copper ions will harm marine organisms. Antimicrobial peptides (AMPs) are a substance extracted from organisms that possess environmental friendliness. This study extracted AMPs from traditional Chinese medicine, analyzed their amino acid sequences, and bound them to the surfaces of cage materials based on the strong adhesion of dopamine in weakly alkaline environments. The Fourier transform infrared spectrometer (FTIR) spectrum results showed that the antibacterial peptide was successfully bound to the substrate surface, and the contact angle results demonstrated a significant change in the wettability of the substrate surface. Antibacterial tests were conducted on the surface of the sample usingStaphylococcus aureus(S. aureus). The results illustrated that 304 stainless steel (SS) and nylon (PA) surfaces modified by the antibacterial peptide exhibited significant biofilm resistance, with antibacterial adhesion properties reaching 88.68% and 82.61%, respectively, exhibiting the robustness of the antimicrobial efficiency. This study can provide theoretical support for the antifouling performance of the surfaces of marine aquaculture cages.Keywords:marine cage;peptide-modified surface;antimicrobial surface;antibacterial robustness
研究领域:
生物学
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海洋科学
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材料科学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2019
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IF 8.456
Sen Lin,Chaoxiang Ge,Doudou Wang,Qi Xie,Biao Wu,Jingjie Wang,Kaihui Nan,Qinxiang Zheng,Wei Chen
The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.
研究领域:
药剂学
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眼科医学
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生物材料
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
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IF 8.456
Jie Yin,Dajing Yao,Guangfu Yin,Zhongbing Huang,Ximing Pu
Magnetic resonance imaging (MRI) is widely applied in medical research and diagnosis, and a MRI contrast medium plays a crucial role in improving the sensitivity of detection. Ultrasmall superparamagnetic iron oxides (USPIOs) exhibit the potential as a T2 enhancement contrast medium for MRI due to their excellent magnetic response performance; however, to endow them with specific tumor targetability, long-term circulation performance has always been a hot topic in this field. In this study, a well-designed procedure of chemical coprecipitation, surface modification, and peptide grafting was applied to prepare the active tumor-targeting USPIOs@F127-WSG, in which Pluronic F127 (F127) and the peptide WSGPGVWGASVK (peptide-WSG) were selected as the template agent and the ovarian tumor-targeting ligand, respectively. The results showed that single USPIOs@F127-WSG particles were Fe3O4 nanoparticles regulated by the confinement effect of F127 micelles with a uniform globular morphology and size (∼9 nm), and peptide-WSG was grafted for their tumor targetability. USPIOs@F127-WSG particles presented superparamagnetic behavior with high T2 relaxivity (r2 = 278.15 mM–1 s–1) and in vitro targetability for SKOV-3 cells due to the special binding between peptide-WSG and specific receptors of SKOV-3. The test results in vivo verified the targetability of USPIOs@F127-WSG by their specific aggregation in the tumor regions, leading to the T2-weighted MRI contrast enhancement. These outstanding properties indicate that USPIOs@F127-WSG have great potential to be applied as the active tumor-targeting contrast agent for MRI.
研究领域:
医学影像学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLUSTER SCIENCE
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2018
·Vol. 29
·期 3
·469-473
·
IF 1.715
Zhang Zhengyu,Yuan Ailin,Chen Chan,Zheng Chunling,Xu Hong
We have obtained a kind of simple and highly effective method for detection of calcium ions based on glutathione functionalized gold nanoparticles (GSH-GNPs) in this article. The GSH-GNPs can be induced to aggregate immediately in the presence of calcium ions that can be detected by colorimetric response of GNPs monitored by a UV–vis spectrophotometer or even naked eyes, and the detection limit could reach 20 μM. Compared to other metal ions, the GSH-GNPs bound by calcium ions shows higher sensitivity with prominent color changes. Most importantly, the probe not only can be tested the content of calcium ion in the water simply and effectively, but also can be applied to estimate calcium levels in blood with low interference and high sensitivity.
研究领域:
分析化学
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生物医学
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产品关联
DOI
高影响因子
Journal of Environmental Chemical Engineering
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2024
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IF 7.4
Liwen Wang,Guang Wu,Tengfei Wang,Dating Tian
Organophosphorus pesticides (OPs) are commonly employed in agriculture because they effectively control pests and increase crop output. However, most OPs are highly toxic. As a result, precise detection of OPs residues is critical for monitoring human disease and protecting the environment. In this work, we developed an aggregation-induced emission (AIE) probe of Sm-GSH-CuNCs for sensitive and visual detection of OPs by combining Sm 3+ with glutathione-modified copper nanoclusters (GSH-CuNCs). Using glyphosate as the OPs model, the fluorescence of GSH-CuNCs was quenched due to the stronger affinity between Sm 3+ and glyphosate than that between Sm 3+ and GSH-CuNCs, as well as the formation of new P-O-Sm bonds between Sm 3+ and glyphosate , resulting in the "on-off" response of the AIE probe. The Sm-GSH-CuNCs probe detected glyphosate throughout a linear range of 0.338–5.070 mg/L, with a detection limit of 0.013 mg/L. Furthermore, we have constructed an Sm-GSH-CuNCs agar slice detection platform that used smartphone assistance to detect glyphosate visually and quantitatively. A good linear relationship between R/B values and OPs concentrations( C i ) was discovered: R/B =-0.316 C i +1.943 ( R 2 =0.9970). This work provided a simple, low-cost, and portable detection method for quantifying or visualizing OPs.
研究领域:
分析化学
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环境科学
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农业科学
✓ 已验证
产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
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2024
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IF 4.5
Qingqing Zhang,Zeyu Yang,Jie Zhang,Yanchen Li,Xintao Dang,Jingkun Qu,Xiaoyan Pan,Jie Zhang
In recent years, targeting tumor angiogenesis has emerged as a prominent research focus in the treatment and prevention of tumor expansion. A7R (ATWLPPR) exhibits high affinity and specificity for VEGFR-2, which is overexpressed in various tumors. To enhance the tumor tissue and cell penetration capabilities of A7R, we substituted its non-critical amino acid with Arginine (R) and Glutamic acid (E), cyclized the mutant peptide, and linked it to the membrane permeation sequence using coordination principles. We designed and synthesized fifteen novel penetrating peptides that target tumor blood vessels and cells, followed by conducting various biological evaluations and cell imaging experiments. The results demonstrated that Cyclo-A7R-RRR and A7R-RLLRLLR exhibited excellent permeability towards tumor cells, with Cyclo-A7R-RRR showing superior serum stability compared to A7R. Furthermore, the modified peptides showed no toxicity towards HeLa cells, U251 cells, HuH-7 cells, and HEK293 cells under 10 μmol/L. Utilizing Cyclo-A7R-RRR or A7R-RLLRLLR for transmembrane delivery of drug molecules could significantly improve their efficacy. Our findings broaden the potential application scenarios of A7R in targeted tumor angiogenesis.
研究领域:
癌症研究
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分子生物学
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药学
✓ 已验证
DOI
PubMed
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
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2021
·
IF 5.455
Rui Li,Xianbin Mei,Xiangfeng Li,Changli Zhang,Liping Ruan
A novel bolt-like-blocking nanovalve based on mesoporous silica nanoparticles (MSNs) has developed as a drug carrier, using the modified short peptide as a support and the delivery drug as a bridge for fulfilling the blocking process. The peptide-modified nanoparticle MSN-S-S-NAC-Trp combined with the loaded drug can be used as a carrier with no leakage and be triggered for release by appropriate GSH. The peptide-modified nanoparticles have showed no obvious cytotoxicity and can be internalized into L929 cells; moreover, the doxorubicin loaded nanoparticles incubated with HeLa cells have showed GSH-responsive capability and induced cell apoptosis. Since the chain of the modified peptide on the surface of MSN is not long enough to block the channel via self-assembly process, a bolt-like-blocking model is proposed.
研究领域:
纳米医学
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药物递送系统
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生物材料
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Na Liu,Yanan Tan,Yingwen Hu,Tingting Meng,Lijuan Wen,Jingwen Liu,Bolin Cheng,Hong Yuan,Xuan Huang,Fuqiang Hu
Redox-responsive nanomaterials applied in drug delivery systems (DDS) have attracted an increasing attention in pharmaceutical research as a carrier for antitumor therapy. However, there would be unwanted drug release from a redox-responsive DDS with no selection at nontarget sites, leading to undesirable toxicities in normal tissues and cells. Here, an A54 peptide modified and PEGylated reduction cleavable glucolipid conjugate (A54-PEG-CSO-ss-SA, abbreviated to APCssA) was designed for intracellular delivery of doxorubicin (DOX). The synthesized APCssA could be assembled via micellization self-assembly in aqueous water above the critical micelle concentration (54.9 μg/mL) and exhibited a high drug encapsulation efficiency (77.92%). The APCssA micelles showed an enhanced redox sensitivity in that the disulfide bond could be degraded quickly and the drug would be released from micelles in 10 mM levels of glutathione (GSH). The cellular uptake studies highlighted the affinity of APCssA micelles toward the hepatoma cells (BEL-7402) compared to that toward HepG2 cells. In contrast with the nonresponsive conjugate, the drug was released from APCssA micelles more quickly in 10 mM level of GSH concentration (tumor cells). Moreover, the DOX-loaded APCssA micelles displayed an increased cytotoxicity which was 1.6- to 2.0-fold that of unmodified and nonresponsive micelles. In vivo, the APCssA micelles had stronger distribution to liver and hepatoma tissue and prolonged the circulation and retention time, while the drug release only occurred in the tumor tissue. The APCssA/DOX showed the tumor inhibition rate equal to that of commercial doxorubicin hydrochloric without negative consequence. This study suggested that the APCssA/DOX showed promising potential to treat the tumor for its special tumor targeting, selective intracellular drug release, enhanced antitumor activity, and reduced toxicity on normal tissues.
研究领域:
药学
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2023
·
IF 5.2
De-Yan Qi,Chong Wang,Qi-Yu Liang,Hong-Wei Li,Yuqing Wu
In the present study, glutathione-capped gold nanoclusters (AuNCs@GSH) were prepared by an improved hydrothermal method , which showed near-infrared (NIR) emission centered at 805 nm. Besides, Ag + can induce the NIR emission transformations in a two-stage mode under different concentration ranges of Ag + . At the first stage (0.50–15 μM), a new emission at 615 nm was generated while the original NIR emission was quenched upon Ag + addition; at the second stage (15–120 μM), it shifted to 720 nm gradually along with more Ag + addition, which realized precise regulation of the emission range of metal nanoclusters from red to NIR region. The in-depth mechanism investigation revealed the transformations in both stages originated from the anti-galvanic reaction (AGR) of AuNCs toward Ag + and Ag deposition. In detail, the first stage was attributed to the formation of bimetallic gold and silver nanoclusters (Au-AgNCs); while the second stage ascribed to the Ag deposition-induced size growth and composition changes of Au-AgNCs. Therefore, the present study supplies a simple and rapid method for preparing NIR-emitted AuNCs and provides a facile approach to regulate the photoluminescence ranges based on the AGR and Ag deposition.
研究领域:
纳米材料科学
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分析化学
·
光致发光材料
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Jingmou Yu,Liangliang Wang,Yun Ling,Xin Xiao,Juntao Gong,Hongguang Jin,Jing Xu,Pu Chen,Xin Xie,Lei Zhang
Triple-negative breast cancer is an offensive tumor that is highly challenging to cure. In this study, we developed novel polymeric nanoparticles that target dual receptors and respond to reducing conditions for chemotherapeutic drug release in the treatment of triple-negative breast cancer. Then we synthesized and characterized a targeted peptide-grafted chondroitin sulfate A-ss-deoxycholic acid (TCSSD) copolymer and prepare doxorubicin (DOX)-loaded TCSSD (TCSSD-D) micelles high-loading content. The bioresponsive drug release of TCSSD-D nanoparticles was demonstrated in a glutathione-containing phosphate buffer solution . We found that TCSSD-D effectively targeted CD44 and P-selectin receptors both in vitro and in vivo . TCSSD-D micelles were higher cytotoxicity and cellular uptake than unmodified DOX-containing micelles in MDA-MB-231 cells. Furthermore, TCSSD-D micelles showed the strongest suppression of tumor growth among three DOX-based formulations in triple-negative MDA-MB-231-bearing nude mice . These results suggest that amphiphilic TCSSD nanoparticles can serve as a targeted and intelligent delivery vehicle for triple-negative breast cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）