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MICROCHIMICA ACTA · 2020 ·Vol. 187 ·期 6 ·1-9 · IF 6.232

Monodispersed mesoporous SiO2@metal-organic framework (MSN@MIL-101(Fe)) composites as sorbent for extraction and preconcentration of phytohormones prior to HPLC-DAD analysis

Qin Peige,Zhu Wenli,Han Lizhen,Zhang Xiaowan,Zhao Bing,Zhang Xuebin,Lu Minghua

The monodispersed mesoporous SiO 2 @metal-organic framework (MSN@MIL-101(Fe)) composites were prepared by grafting MSN-NH 2 onto MIL-101(Fe) particles with a solvothermal method. The adsorption ability of the composites was greatly improved compared to that of pristine MSNs or MIL-101(Fe) for phytohormones (Phys). The MSN@MIL-101(Fe) composites were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive spectrometer, and mapping analysis. Using MSN@MIL-101(Fe) composites as sorbent, a dispersive solid-phase extraction procedure (dSPE) was developed to extract three endogenous Phys (abscisic acid (ABA), indole-3-aceticacid (IAA), and indole-3-butyric acid (IBA)) and two exogenous Phys (1-naphthylacetic acid (1-NAA) and 2-naphthylacetic acid (2-NAA)) prior to HPLC-DAD analysis. The experimental parameters including sample volume, sorbent amount, adsorption time, adsorption pH, desorption time, and desorption solvent on extraction efficiency were optimized and evaluated. Under optimized conditions, the working range of 0.08 to 0.45 ng mL −1 with enrichment factors from 144 to 207 were achieved. The linear range is 0.75–200 ng mL −1 for IAA, 0.20–200 ng mL −1 for ABA, and 1.0–200 ng mL −1 for IBA, 1-NAA, and 2-NAA. With MSN@MIL-101(Fe) as sorbent for extraction of Phys and determination by HPLC-DAD, two endogenous Phys (IAA and ABA) were detected from mung bean sprouts which were made in a laboratory, and the results were further confirmed by high-resolution mass spectrometry. The composites can be applied to extract other small molecules, which have similar chemical structures with Phys in biological, environmental, and food samples. Schematic presentation of a dispersive solid-phase extraction using monodispersed mesoporous SiO 2 @metal-organic framework composites (MSNs@MIL-101(Fe)) as the sorbent for extraction, clean-up, and preconcentration of phytohormones in mung bean sprouts prior to HPLC-DAD analysis.

研究领域: 分析化学 · 植物学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Intelligent Nanoplatform with Multi Therapeutic Modalities for Synergistic Cancer Therapy

Linjie Shao,Taishun Hu,Xingyu Fan,Xiaozan Wu,Fangfang Zhou,Botao Chen,Songwen Tan,Hui Xu,Anqiang Pan,Shuquan Liang,Yongju He

Chemodynamic therapy (CDT) has attracted increasing attention in tumor treatment but is limited by insufficient endogenous H2O2. Moreover, it is challenging for monotherapy to achieve a satisfactory outcome due to tumor complexity. Herein, we developed an intelligent nanoplatform that could respond to a tumor microenvironment to induce efficient CDT without complete dependence on H2O2 and concomitantly generate chemotherapy and oncosis therapy (OT). The nanoplatform was constructed by a calcium- and iron-doped mesoporous silica nanoparticle (CFMSN) loaded with dihydroartemisinin (DHA). After entering into cancer cells, the nanoplatform could directly convert the intracellular H2O2 into toxic •OH due to the Fenton-like activity of CFMSN. Meanwhile, the acidic microenvironment and endogenous chelating molecules triggered Ca2+ and Fe3+ release from the nanoplatform, causing particle collapse with accompanying DHA release for chemotherapy. Simultaneously, the released Ca2+ induced intracellular Ca2+-overloading for OT, which was further enhanced by DHA, while the released Fe3+ was reduced to reactive Fe2+ by intracellular glutathione, guaranteeing efficient Fenton reaction-mediated CDT. Moreover, Fe2+ cleaved the peroxy bonds of DHA to generate C-centered radicals to further amplify CDT. Both in vitro and in vivo results confirmed that the nanoplatform exhibited excellent anticancer efficacy via the synergistic effect of multi therapeutic modalities, which is extremely promising for high-efficient cancer therapy.

CAS / MDL: 4091-99-0 359010-70-1
研究领域: 纳米技术 · 癌症研究 · 治疗学 · 材料科学
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International Journal of Nanomedicine · 2023 · IF 8

A Novel pH-Responsive Iron Oxide Core-Shell Magnetic Mesoporous Silica Nanoparticle (M-MSN) System Encapsulating Doxorubicin (DOX) and Glucose Oxidase (Gox) for Pancreatic Cancer Treatment

Guiqiang Qi,Guangyue Shi,Shengchao Wang,Haifeng Hu,Zhichen Zhang,Qiangqiang Yin,Zhongtao Li,Liguo Hao

Introduction This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.

研究领域: 药剂学 · 肿瘤学 · 生物医学工程
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NEW JOURNAL OF CHEMISTRY · 2019 ·Vol. 43 ·期 6 ·2694-2701 · IF 3.069

Folate-targeting and bovine serum albumin-gated mesoporous silica nanoparticles as a redox-responsive carrier for epirubicin release

Yuan Zhang,Yang Xing,Ming Xian,Shaomin Shuang,Chuan Dong

Herein, distinctive nanomaterial-based mesoporous silica nanoparticles (MSNs) successively coupled with bovine serum albumin (BSA) and folic acid (FA) were engineered for targeting the release of epirubicin (EPI). The BSA molecule as a “gatekeeper” prevents untimely drug leakage until the BSA coating layer is biodegraded in response to GSH. FA promotes the specific intracellular delivery of the drug to high folate receptor (FR)-expressing cancer cells to improve the efficacy of chemotherapy. In vitro drug release profiles show that this drug carrier can avoid premature release of the drug under physiological conditions, and redox-responsive EPI release from EPI/MSN-FA with easy biodegradability is significantly accelerated in the presence of GSH due to the cleavage of the intramolecular disulfide bond; thus, a “redox-triggered release” of the drug in the simulated targeted tissue microenvironment is achieved. The folate-mediated cellular uptake measured by confocal laser scanning microscopy (CLSM) shows that the hybrid nanoparticles more likely enter the FR-positive (FR+) HepG2 cells than the FR-negative (FR−) PC-12 cells. Toxicity experiment also demonstrates the negligible toxicity of MSN-FA and an increase in the antitumor suppression of EPI/MSN-FA with an increase in the dosage. The results show that the strategy of combining mesoporous silica with protein molecules having stimuli-responsive biodegradability will offer new potential directions towards the “on-demand” drug release for pinpoint chemotherapy in cancer treatment.

研究领域: 纳米技术 · 药学 · 癌症研究 · 药物递送系统 · 生物医学工程
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

NIR-triggered and Thermoresponsive Core-shell nanoparticles for synergistic anticancer therapy

Hong Zhang,Xiao Wang,Xiaorong Yang,Zehua Wu,Qin Chen,Qiaolin Wei,Yong Guo,Quan Hu,Jia-Wei Shen

Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a “gatekeeper”, enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications.

CAS / MDL: 298-93-1
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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JOURNAL OF CHROMATOGRAPHY A · 2018 · IF 3.716

Screening and identification of ligand-protein interactions using functionalized heat shock protein 90-fluorescent mesoporous silica-indium phosphide/zinc sulfide quantum dot nanocomposites

Zhaoyi Miao,Yue Hu,Xiaojing Zhang,Xiaotong Yang,Yingying Tang,An Kang,Dong Zhu

Currently, nanosphere-based ligand fishing cannot be accomplished with imaging processing, although this step is important for real-time identification. Herein, a ligand fishing technique combined with real-time imaging is presented for the identification of ligands for heat shock protein 90α (Hsp 90α) from a complex matrix, Alisma plantago-aquatica Linn . crude extract, using Hsp 90α-functionalized mesoporous silica nanoparticle (MSN)-InP/ZnS quantum dot (QD) nanocomposites as a support material. Twenty ligands for Hsp 90α were screened, and their structures were identified by mass spectrometry. The activities of the ligands were verified by real-time imaging of cells apoptotic morphological changes. Quantitative analysis showed that Alisma plantago-aquatica Linn contained 8.19   μg/g Alisol F, which regarded as one typical component of Alisma plantago-aquatica Linn , and the extraction ratio of Alisol F was 76.2%. The precision for five replicate measurements was 7.0% (RSD). The prepared nanocomposites were also used to screen proteins from a mixture of cellular extracts, and five proteins from HeLa cells were identified as potential client proteins of Hsp 90α.

CAS / MDL: 108-67-8 78-10-4
研究领域: 纳米技术 · 生物化学 · 药学 · 分子生物学 · 分析化学
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MOLECULES · 2014 ·Vol. 19 ·期 4 ·4857-4879 · IF 2.095

Identification of Absorbed Constituents in the Rabbit Plasma and Cerebrospinal Fluid after Intranasal Administration of Asari Radix et Rhizoma by HS-SPME-GC-MS and HPLC-APCI-IT-TOF-MSn

Chen Li,Feng Xu,De-Mei Xie,Yu Jing,Ming-Ying Shang,Guang-Xue Liu,Xuan Wang,Shao-Qing Cai

Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat numerous diseases for over two millennia. It has many advantages compared with other routes. In this article, headspace-solid phase microextraction-gas chromatography-mass spectrometry and high performance liquid chromatography-atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass spectrometry were applied for the first time to analyze the absorbed constituents in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14 monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nineN-alkylamides and eight lignans were tentatively identified in the rabbit plasma and CSF. Thirty-three absorbed constituents are found to have different bioactivities related to the pharmacological actions of AR through bibliography data retrieval. These indicated that many types of constituents of TCM can be absorbed at the nasal cavity into both rabbit blood and CSF. This is the first study to explore the absorption of AR, and comprehensively analyze the absorbed constituents after intranasal administration of TCM. These findings extend our understanding of the effective substances of AR, and inspire us to make a hypothesis on the mechanism of additive effect of multiple constituents of TCMs, which is very worthy of further investigation.Keywords:nasal therapy;Asarum heterotropoidesvar.mandshuricum;intranasal administration;effective substance;cerebrospinal fluid;absorption;SPME;GC-MS;LC-MS;additive effect

CAS / MDL: 6443-69-2
研究领域: 中药学 · 分析化学 · 药理学
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Journal of Pharmaceutical Innovation · 2025 ·Vol. 20 ·期 6 ·1-17 · IF 2.7

Isolation and Characterization of a Novel Photo-Degradant of Brexpiprazole Due to an Intramolecular [2 + 2] Cycloaddition Via High Resolution MSn (n = 1 To 3) Analysis and Multi-Dimensional NMR Measurement

Lin Jinsheng,Wu Qilin,Liu Xueyang,Cao Renjian,Yong Qiyun,Li Dan,Chen Wenbin,Li Min,Shen Weiyang

Purpose This study intended to investigate two unknown impurity peaks (DP-1 and DP-2, at 0.29% and 0.20%, respectively) observed during the stability testing of brexpiprazole drug substance, which exceeded the unspecified impurity threshold (≤ 0.10%) and triggered an out-of-specification (OOS) investigation in a GMP environment. The objectives are to identify their structures, determine whether they are true impurities or artificial degradants, and establish appropriate control procedures for the pharmaceutical analysis of brexpiprazole. Methods The impurities were initially characterized using LC-UV/PDA high-resolution MS n ( n  = 1 to 3), which identified DP-1 as an isomer of brexpiprazole and DP-2 as a dimer. Further structural elucidation of DP-1 was performed using semi-preparative HPLC and 1D/2D NMR spectroscopy. Forced degradation studies were conducted under photolytic conditions to confirm the formation of DP-1 and DP-2, with freshly prepared solutions kept in the dark as controls. Results DP-1 and DP-2 are both photo-degradants of brexpiprazole in solution. DP-1 is confirmed as an intramolecular [2 + 2] cycloaddition product of brexpiprazole, which is a novel and unreported impurity found in the product of brexpiprazole. DP-2 is identified as an intermolecular [2 + 2] cycloaddition product and consistent with a prior literature [ 1 ]. Both impurities formed only under light exposure and were absent in the light-protected samples, confirming their photodegradation origin rather than inherent impurities. Conclusion Both DP-1 and DP-2 are photo-induced degradants of brexpiprazole, rather than real impurities. These findings enhance understanding of brexpiprazole’s degradation chemistry and emphasize the need for light-protected sample preparation to prevent artifactual peaks in pharmaceutical analysis of brexpiprazole drug substance and its formulations.

CAS / MDL: 17084-13-8
研究领域: 药物化学 · 分析化学 · 药物稳定性 · 杂质谱分析 · 质谱分析 · 核磁共振(NMR)
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Materials Today Chemistry · 2022 · IF 7.613

Friction-induced supramolecular nanovalves for the potential treatment of osteoarthritis

Q. Wang,X. Yu,Y. Zhao,Y. Wang,K. Chen,Y. Liu,B. Wang,H. Zhang,Y. Sun

Owing to the overuse of rough articular cartilage, it increases the friction of joint and further leads to inflammation in joint cavities. However, the pathological changes also bring a new opportunity to achieve the treatment of osteoarthritis (OA). The increasing friction from damaged articular cartilage can convert more mechanical energy to heat. The higher localized temperature can reduce supramolecular interactions in general. Therefore, friction becomes another new activation to operate nanovalve systems for the targeting treatment of OA. Here, we designed and prepared a friction-induced nanovalve system constructed with β-cyclodextrins (β-CD)-modified mesoporous silica nanoparticles (MSN). Besides, a copolymer containing two components – guest molecules (adamantane, AD) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) – has been self-assembled on the surface of β-CD-modified MSN (MSN-CD) by supramolecular host–guest interactions. In this design, the charged PMPC on the MSN surface can form a dense hydration layer by ion–dipole interactions, switch the friction from surfaces to water molecules to achieve hydration lubrication , and sharply reduce the coefficient of friction (COF). Besides, the higher localized temperature from the mechanical conversion can weaken the supramolecular host–guest interactions and turn on the nanovalves to accomplish the targeted release near rough articular cartilage of OA. Even when PMPC is peeled off, the hydrophilic surface of β-CD on MSN surface can still perform the acceptable lubricating properties. The following testings of cytotoxicity by CCK-8 and live/dead staining indicated the excellent biocompatibility. Further analysis of protein expression levels has also shown the potential application in OA.

CAS / MDL: 814-68-6 768-94-5
研究领域: 纳米技术 · 生物材料 · 药物递送系统 · 生物医学工程 · 骨科
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Applied Materials Today · 2024 · IF 7.2

Ti3C2Tx MXene nanosheet-based drug delivery/cascaded enzyme system for combination cancer therapy and anti-inflammation

Qianqian Qiao,Jinyu Wang,Bingjiao Li,Yuhao Guo,Tao Liao,Ziqiang Xu,Ying Kuang,Cao Li

Photothermal therapy (PTT)-based combination therapy is an effective approach to cancer treatment. However, there is a possibility of tumor development due to the inflammation caused by PTT. In addition, hyperthermia can cause damage to normal tissues. This work reported a drug delivery/cascade enzyme system based on Ti 3 C 2 T x MXene nanosheets. Ultra-small, degradable mesoporous silica nanoparticles (DS-MSN) were prepared to load phloretin (Phl), which has anti-inflammatory, antioxidant, and anticancer properties. Subsequently, glucose oxidase (GOx) was adsorbed on the surface of DS-MSN. The nanoparticles were then modified on Ti 3 C 2 T x MXene nanosheets and finally treated with polyethylene glycol (PEG) to obtain the multifunctional system named Ti 3 C 2 T x -Phl@DS-MSN-GOx-PEG (TPDMGP). The high near-infrared photothermal conversion efficiency of Ti 3 C 2 T x made it suitable for PTT. GOx and Ti 3 C 2 T x formed a cascade enzyme system inside cancer cells: Ti 3 C 2 T x exhibited catalase (CAT)-like activity that decomposed intracellular hydrogen peroxide (H 2 O 2 ) into O 2 , which was provided to GOx for enhanced starvation therapy. GOx in the presence of O 2 produces H 2 O 2 , for the oxygen production of Ti 3 C 2 T x . Meanwhile, DS-MSN could be degraded in the reducing environment inside cancer cells as it contains disulfide bonds in its backbone, thus releasing Phl for chemotherapy. Such a combination therapy strategy could achieve a satisfactory therapeutic outcome by low-temperature PTT while evading normal tissue damage by high temperature. The anti-inflammatory effects of both Ti 3 C 2 T x and Phl enabled TPDMGP to eliminate the inflammation caused by PTT via the scavenging of reactive oxygen species (ROS). The multifunctional system is expected to generate new paradigms for cancer PTT.

CAS / MDL: 919-30-2
研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 酶工程 · 材料科学
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

pH-responsive theranostic nanoplatform of ferrite and ceria co-engineered nanoparticles for anti-inflammatory.

Yuanyao Dou,Yimin Zhang,Caiyu Lin,Rui Han,Yubo Wang,Di Wu,Jie Zheng,Conghua Lu,Liling Tang,Yong He

Multiple component integration to achieve both therapy and diagnosis in a single theranostic nanosystem has aroused great research interest in the medical investigator. This study aimed to construct a novel theranostic nanoplatform ferrite and ceria co-engineered mesoporous silica nanoparticles (Fe/Ce-MSN) antioxidant agent though a facile metal Fe/Ce-codoping approach in the MSN framework. The resulted Fe 3+ -incorporated ceria-based MSN nanoparticles possessing a higher Ce 3+ -to-Ce 4+ ratio than those revealed by ceria-only nanoparticles. The as-prepared Fe/Ce-MSN nanoparticles exhibited an excellent efficiency in scavenging reactive oxygen species (ROS), which is attributed to improving the superoxide dismutase (SOD) mimetics activity by increasing Ce 3+ content and maintaining a higher activity of catalase (CAT) mimetics via including ferrite ion in nanoparticles. The fast Fe/Ce-MSN biodegradation, which is sensitive to the mild acidic microenvironment of inflammation, can accelerate Fe/Ce ion release, and the freed Fe ions enhanced T 2 -weighted magnetic resonance imaging in the inflammation site. PEGylated Fe/Ce-MSN nanoparticles in vitro cell models significantly attenuated ROS-induced inflammation, oxidative stress, and apoptosis in macrophages by scavenging overproduced intracellular ROS. More importantly, Fe/Ce-MSN-PEG NPs exhibited significant anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) levels in vitro . Additionally, it can promote the macrophages polarization of pro-inflammatory M1 phenotype towards an anti-inflammatory M2 phenotype. Thus, the novel pH-responsive theranostic nanoplatform shows great promise for inflammation and oxidative stress-associated disease treatment.

CAS / MDL: 9004-74-4 2258654-78-1
研究领域: 纳米技术 · 材料科学 · 生物医学工程 · 药学 · 炎症研究
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