RSC Advances
·
2016
·Vol. 6
·期 104
·102398-102405
·
IF 3.289
Yuxi Liu,Siwen Li,Dan Chen,Zhaohui Wang,Jinnan Zhang,Caiping Tian,Li Ding,Yaqi Chen,Zhiyu Qian,Yueqing Gu
The existence of EML4–ALK, a mutated fusion gene in non-small-cell lung cancer (NSCLC), is an important consideration in the decision of the treatment options for NSCLC patients. However, there has been no standardized methods for EML4–ALK fusion gene detection up to now, which makes the development of novel detection probes particularly appealing. A molecular beacon is effective in detecting the level of a particular mRNA in living cells with easy signal visualization and convenient application. In this study, a molecular beacon composed of a gold nanoparticle core densely packed with FITC-labeled hairpin DNA sequences was synthesized and characterized. The presence of the EML4–ALK fusion gene will specifically open the hairpin structure, leading to the recovery of FITC fluorescence. This molecular beacon could precisely distinguish NSCLC cell lines with different levels of EML4–ALK mRNA expression, as indicated by obvious fluorescence in the EML4–ALK positive H2228 cell line and a negligible signal in the negative A549 cell line. The sensitivity and specificity of the molecular beacon were further verified in H2228 cells treated with small interfering RNAs (siRNAs) against ALK, which demonstrated decreased fluorescence after gene silencing. These results were simultaneously confirmed by flow cytometry and Q-PCR. More importantly, our molecular beacon successfully identified the EML4–ALK fusion gene in tissue specimens from 2 of 23 NSCLC patients. The results were consistent with Q-PCR quantification. Therefore, this molecular beacon holds great potential in clinical diagnosis of the EML4–ALK fusion gene with remarkable sensitivity and convenience.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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产品关联
DOI
高影响因子
STAR Protocols
·
2020
·
IF 0
Yi Li,Keke Liu,Ying Zhou,Jing Yang,Peng Zou
Summary Alk-Ph is a clickable APEX2 substrate developed for spatially restricted protein/RNA labeling in intact yeast cells. Alk-Ph is more water soluble and cell wall permeable than biotin-phenol substrate, allowing more efficient profiling of the subcellular proteome in microorganisms. We describe the protocol for Alk-Ph probe synthesis, APEX2 expression, and protein/RNA labeling in yeast and the workflow for quantitative proteomic experiments and data analysis. Using the yeast mitochondria as an example, we provide guidelines to achieve high-resolution mapping of subcellular yeast proteome and transcriptome. For complete details on the use and execution of this protocol, please refer to Li et al. (2020) .
研究领域:
分子生物学
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蛋白质组学
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细胞生物学
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生物化学
✓ 已验证
DOI
PubMed
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
·
IF 5.6
Yuan Fan,Yuxiang Liu,Liujiao Wang,Huashan Xu,Lele Yu,Yue Lang,Huafei Li,Fuxue Chen,Shini Feng
Protein hydrolysis-targeted chimeras (PROTACs) are heterobifunctional molecules designed for the selective degradation of target proteins. MS4078, a novel PROTAC, shows promise for treating ALK-positive non-small cell lung cancer (NSCLC), yet its clinical efficacy is hindered by suboptimal tumor targeting and off-target toxicities. To enhance its therapeutic profile, we developed human heavy chain ferritin (HFN) as a targeted delivery system, leading to the creation of HFN@MS4078 nanocages. Prepared via passive loading, HFN@MS4078 achieved a drug loading capacity of 178 molecules per nanocage with a HFN recovery rate of 70.1 %. The nanocages exhibited a rapid release profile under lysosomal conditions (pH 5.0), with approximately 80 % drug release after 60 h, while maintaining over 80 % stability at physiological pH 7.4. In vitro, HFN@MS4078 was actively internalized into lysosomes via TfR1 receptor binding, resulting in a 2.7–2.8 times reduction in IC 50 values compared to free MS4078. Furthermore, HFN@MS4078 significantly decreased the expression levels of ALK, p-ALK, p-AKT, and p-ERK in NCI-H2228 and NCI-H3122 cell lines. In vivo, HFN@MS4078 substantially reduced tumor volume and prolonged survival while exhibiting negligible systemic toxicity. These results suggest that HFN@MS4078 represents a promising strategy for targeted therapy in ALK-positive NSCLC, enhancing therapeutic efficacy while minimizing systemic toxicity.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
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药物递送
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 4.7
Zhen-Peng Yu,Ke-Xin Sun,Dan Zhang,Zhi-Qiang Yu,Deng-Yun Chen,Hong Zhu,Hongwei Si,Peng-Fei Dai
Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer 68 Ga-DOTA-CTB ( 68 Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The 68 Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that 68 Ga-DOTA-CTB could be accumulated in H2228 cells. Imaging and biodistribution experiments have revealed significant uptake of the radiotracer in the tumors of the experimental group, while tumors in the blocking group, which were saturated with an excess of precursor, exhibited a markedly reduced level of radioactivity. These empirical findings suggest that 68 Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.
研究领域:
肿瘤学
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核医学
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分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2015
·
IF 0.633
Haidong Liu,Yuan Li,Dongdong Wang,Yu Qin,Min Ji
A convenient route for the synthesis of Novartis's second-generation anaplastic lymphoma kinase inhibitor Ceritinib (LDK378) involving starting materials that are commercially available has been achieved. The procedure employed mild reaction conditions and avoided the use of expensive reagents compared to the original synthetic route reported by Novartis. More importantly, gram scale synthesis was accomplished and this protocol could be valid in drug discovery synthesis.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jiadong Pang,Xiaoyu Chen,Zhijun Lin,Shuo Yao,Wanyan Wang,Hong Wu,Wei Xing,Jiang Yang
Anaplastic lymphoma kinase (ALK) oncogenic fusions are an infamously evolving target in ALK fusion-positive (ALK + ) non-small cell lung cancer (NSCLC). RNA interference (RNAi) is a potential alternative to small-molecule ALK inhibitors but suffers from poor cellular delivery and low stability, restricting sustained on-target therapeutic efficacy. To attain non-invasive direct RNAi at target sites in the lungs, inhalable vehicles are demanded to shield unstable siRNA from degradation in alkaline pleural fluid and to shuttle siRNA in the acidic tumor microenvironment. Here, we chemically synthesize a universal polyethylene glycol-poly(β-amino esters)-histidine(PEG-PBAE-His, PPH) system that enables siRNA-directed ALK gene silencing in ALK + NSCLC with controlled release. The rational design of PEGylated polycationic PPH integrates the non-ionic nature, inertness, stealth effect, and low immunogenicity of PEG coronae with dual positively-charged PBAE and His to encapsulate siRNA payloads through enhanced electrostatic complexations. The assembled polyplexes with low polydispersity are overall anionic in alkaline pleural fluid and reversed into cationic charges at acidic pH, facilitating cellular uptake and lysosomal pH-governed release. The PPH-directed delivery significantly improves siRNA stability and ALK sequence-specific knockdown in H3122 cells, with a transfection efficiency comparable to commercial polyethylenimine but with lower cytotoxicity. The ALK-centric RNAi therapy prohibits cancer clonogenicity, migration, and invasion and induces potent growth inhibition in ALK + NSCLC xenografts through inhalation. The inhalable polyplexes represent a transformative delivery platform that combines pH-responsive targeting, enhanced stability, and low toxicity, addressing critical limitations of existing siRNA delivery systems.
研究领域:
肿瘤学
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分子生物学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2021
·
IF 8.198
Feng Yao,Shuyan Guan,Linyan Bian,Yanping Fan,Xianyun Liu,Huanhuan Zhang,Baojun Li,Baozhong Liu
Creating active sites to improve the mass activity and durability of metal catalysts by elucidating the relationship between the metal and the support is a major challenge. In this study, ultrafine palladium nanoparticles (Pd NPs) were supported on alkalized Ti3C2 (alk-Ti3C2) to obtain a catalytically active interfacial ensemble. The catalyst Pd/alk-Ti3C2 with a Pd loading of 1.0 wt % exhibited the highest activity in ammonia borane (AB) hydrolysis reaction, with an initial turnover frequency of 230.6 min–1. A comprehensive analysis revealed that an ensemble-exciting effect originated from the Pd and the alk-Ti3C2. The hydroxylation of alk-Ti3C2 regulated the local coordination environment of Pd. Water and AB were effortlessly activated by the −OH group and Pd atom aggregates composed of electron-deficient support alk-Ti3C2 and electron-rich Pd, respectively. The efficient generation of hydrogen at the interface of Pd/alk-Ti3C2 was further guaranteed by the interfacial activation. This work on precision active sites opens new avenues for developing high-activity noble-metal catalysts for AB hydrolysis.
研究领域:
催化化学
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材料科学
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能源化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yanan Xiao,Qi Pu,Chenxing Wang,Xiaoteng Jia,Shixiang Sun,Quan Jin,Xiaolong Wang,Bin Wang,Peng Sun,Fangmeng Liu,Geyu Lu
Wearable self-powered pressure sensors present tremendous potential for object recognition. However, the fluctuated approach speed and distance may compromise the device output, thus affecting the recognition accuracy. Herein, a wearable self-powered pressure sensor with high sensitivity (1.48 V kPa −1 ), high output (130.5V), and high permeability (259.98 mm s −1 ) are developed where the contact barrier difference and triboelectric charge density of the triboelectric layer surface are dynamically regulated by modulating the surface groups resulting in a lower dielectric loss and higher output. The sensor leverages the polarity difference between the target object and the sensitive material to generate electrical signals at different speeds and distances through an electrostatic induction mechanism. With the assistance of the Transformer model with a self-attention mechanism, an average recognition accuracy of 94.3% is achieved by acquiring sensing signals at different speeds and distances. Simulating the ability of human vision, enables visually impaired people to acclimate to their surroundings more easily and independently and provides a critical advancement in the assistance of the blind with daily life.
研究领域:
材料科学
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生物医学工程
·
人工智能
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Materials Technologies
·
2021
·Vol. 6
·期 6
·2001157
·
IF 7.848
Yucui Xiang,Liang Fang,Fang Wu,Shufang Zhang,Haibo Ruan,Haijun Luo,Hong Zhang,Wanjun Li,Xingming Long,Baoshan Hu,Miao Zhou
The conflict between high sensitivity and wide sensing range greatly limits the extensive application of flexible pressure sensors. To produce a sensor with both high sensitivity and wide range is still a challenging work. Herein, flexible and highly sensitive piezoresistive sensors with wide sensing range are developed by combining the alkali-treated 3D crinkled MXene with microstructured polydimethylsiloxane (PDMS). Sensors with different-roughness PDMS films as flexible substrate and the unprocessed MXene as the conductive material are prepared to clarify the geometric design for the ultra-wide pressure range (0–800 kPa). Then, other sensors assembled by NaOH-alkalized 3D crinkled MXenes and rough PDMS are fabricated to illustrate that the material optimization can further enhance the sensitivity (up to 1104.38 kPa −1 ). The sensor shows a low limit of detection (17 Pa), fast response time (100 ms), good cycle stability (3000 cycles, 300 kPa), and can detect over a wide pressure range from that of the tiny pills, pulse, heartbeat, throat vibration, and the change of water weight, exhibiting a broad prospect in health monitoring systems and human-machine interaction.
研究领域:
材料科学
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柔性电子学
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传感器与执行器
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纳米材料
·
可穿戴技术
✓ 已验证
DOI
高影响因子
LANGMUIR
·
2025
·
IF 3.9
Bolin Yue,Tingli Wang,Mengke Zhang,Xiaoyu Wu,Xu Xu,Zequan Li,Bohan Ye,Lei Liu,Shiyong Song
Proteolysis-targeting chimeric (PROTAC) technology represents a groundbreaking approach with immense potential for treating a wide range of diseases. However, its clinical application is often limited by challenges in solubility and permeability. Herein, we have developed an innovative three-in-one nanoparticulate therapeutic agent tailored for non-small-cell lung cancer (NSCLC). This agent features a PROTAC molecule derived from ceritinib, designated as 27B, serving as a targeted degrader of anaplastic lymphoma kinase (ALK). 27B is self-assembled with vitamin A palmitate (VAP) and vitamin E poly(ethylene glycol) succinate (TPGS) to form stable nanoparticles (BVT-NPs) that exhibit a uniform spherical morphology, excellent storage stability, and robust plasma stability. With an average particle size of approximately 130 nm and a loading capacity of 27B of 20%, BVT-NPs demonstrate a pH-responsive drug release profile. In vitro studies reveal that BVT-NPs significantly inhibit the proliferation of H3122 cells more effectively than free 27B, indicating a synergistic antitumor effect. Western blot analysis further confirms the superior efficacy of BVT-NPs in downregulating ALK and P-glycoprotein and upregulating Caspase-3. BVT-NPs markedly suppress tumor growth without inducing significant tissue toxicity. This carrier-free, multifunctional nanoparticulate system integrates PROTAC-mediated protein degradation with chemotherapy, thereby improving the PROTAC absorption and generating a synergistic therapeutic effect against NSCLC.
研究领域:
癌症治疗
·
纳米医学
·
药理学
·
生物化学
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Jianbin Zhang,Qiufang Bai,Mei Han,Xizhe Sun,Feixue Zhou,Xin Fang,Yuran Shi,Hongna Wang,Yaowen Zhang,Linwei Li,Linlin Fang
Herein, two highly stable β -CD and α-Alkenyl- β -CD ( α -Alk- β -CD) monolithic columns were fabricated by copolymerizing β -CD and α -Alk- β -CD with GMA onto the pretreated capillary by a simple one-pot strategy. 1 H NMR, SEM, FT-IR, TGA and BET surface area analyses were applied to characterize the prepared monolithic columns. The monoliths were evaluated on the enantioseparations of antibiotic drugs, antihistamine drugs, anticholinergic agents, antifungal drugs and pesticides. In contrast to the native β -CD monolith, the derived α -Alk- β -CD reveals significantly improved enantiodiscrimination performance for the analytes especially for pesticides. Through run-to-run (n = 6), day-to-day (n = 9), and column-to-column (n = 9) investigations, the RSDs values were all lower than 3.72 %. Molecular simulation reveled that the chiral recognition between α -Alk- β -CD and chiral drugs was an exothermic process mainly governed by interaction hydrogen bindings, resulting in different binding strength between a pair of isomers compounds and α -Alkenyl- β -CD, and then leading to different migration and finally achieving effective chiral separation.
研究领域:
分析化学
·
色谱学
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
·
2017
·
IF 9.446
Mei Ming,Yanlin Ren,Min Hu,Yun Zhang,Ting Sun,Yuling Ma,Xiaojing Li,Weidong Jiang,Daojiang Gao,Jian Bi,Guangyin Fan
Exploring MXenes as supports for synthesis of highly efficient catalysts are extremely important for hydrodechlorination of chlorophenols because of the acute toxicity and strong potential bioaccumulation of chlorophenols. We reported a facile strategy to synthesize Rh nanoparticles deposited on 2D alk-Ti 3 C 2 X 2 (X = O, F) (alk-Ti 3 C 2 X 2 for short) MXene, which was prepared through the removal of the Al layers of Ti 3 AlC 2 and post-treatment by alkalization. Modifying the Ti 3 C 2 X 2 support by alkalization triggered the substitution of surface fluorine groups with surface oxygen species. The changes in the surface chemistry of alk-Ti 3 C 2 X 2 effectively prevented particle aggregation to form well-dispersed Rh nanoparticles in small sizes with relative high metal dispersion, thereafter improving the hydrogen uptake capacity of the catalyst. Consequently, the Rh/alk-Ti 3 C 2 X 2 catalyst significantly enhanced the catalytic performance for the HDC reaction, which could be assigned to the large number of active components from small Rh nanoparticles. This strategy provides a basis for investigating the use of MXenes as supports to synthesize well-defined metal nanoparticles in 2D layered structures for potential applications.
研究领域:
环境科学
·
催化化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）