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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2018 · IF 5.091

Nanodiamonds conjugated upconversion nanoparticles for bio-imaging and drug delivery

Kuikui Zhang,Qi Zhao,Shirong Qin,Yang Fu,Runze Liu,Jinfang Zhi,Chongxin Shan

A multifunctional nanoplatform with simultaneous imaging and therapeutic capacities has been fabricated by covalently conjugating nanodiamonds (NDs) with upconversion NaYF 4 :Yb,Er nanoparticles (UCNPs). Green emission can be observed for the UCNP-NDs composites under 980 nm excitation, and in vitro imaging was carried out towards HeLa cells. The UCNP-NDs also shows good drug storage capability toward anticancer drug doxorubicin (Dox) and exhibits significant pH-dependent drug-release behavior. Dox-loaded UCNP-NDs shows higher therapy efficiency towards Hela cells than free Dox when the equivalent concentration of the Dox is more than 10 μg/mL. Thus, a favorable strategy may be provided to decrease the side effects of Dox, minimize drug dose, and improve its efficacy. These findings highlight the fascinating features of UCNP-NDs nanocomposites as upconversion fluorescence imaging contrast agents and doxorubicin loading carrier. In addition, this work may also provide a novel strategy for the design of multifunctional nanoplatforms.

研究领域: 生物医学工程 · 纳米技术 · 药学 · 材料科学
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ANALYTICAL CHEMISTRY · 2023 · IF 7.4

Stretchable Electrochemical Sensor Based on a Gold Nanowire and Carbon Nanotube Network for Real-Time Tracking Cell-Released H2S

Jing Li,Cailing Zhu,Wenjing Peng,Xiaoqing Cao,Hui Gao,Mengyuan Jiang,Zengqiang Wu,Chunmei Yu

Hydrogen sulfide (H2S), as the third gas transporter in biological systems, plays a key role in the regulation of biological cells. Real-time detection of local H2S concentration in vivo is an important and challenging task. Herein, we explored a novel and facile strategy to develop a flexible and transparent H2S sensor based on gold nanowire (AuNW) and carbon nanotube (CNT) films embedded in poly(dimethylsiloxane) (PDMS) (AuNWs/CNTs/PDMS). Taking the advantage of the sandwich-like nanostructured network of AuNWs/CNTs, the prepared electrochemical sensing platform exhibited desirable electrocatalytic activity toward H2S oxidation with a wide linear range (5 nM to 24.9 μM) and a low dete ction limit (3 nM). Furthermore, thanks to the good biocompatibility and flexibility of the sensor, HeLa cells can be cultured directly on the electrode, allowing real-time monitoring of H2S released from cells under a stretched state. This work provides a versatile strategy for the construction of stretchable electrochemical sensors, which has potential applications in the study of H2S-related signal mechanotransduction and pathological processes.

研究领域: 材料科学 · 生物医学工程 · 分析化学 · 细胞生物学
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JOURNAL OF NANOBIOTECHNOLOGY · 2023 ·Vol. 21 ·期 1 ·1-14 · IF 10.2

Superior TRAIL gene expression and cancer cell apoptosis mediated by highly branched-linear poly(β-amino ester)s

Zhao Yitong,Bo Tao,Wang Chenfei,Yao Dingjin,Pan Chaolan,Xu Weiyi,Zhou Hao,Li Ming,Zhang Si

Extensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy. H-LPAEs exhibit a more uniform distribution of linear segments and branching units, leading to excellent DNA condensation and favorable physicochemical properties of H-LPAE/DNA polyplexes. In SW1353 and BMSC cells, the optimized H-LPAEs, H-LPAE B4−S5−TMPTA , achieves superior gene transfection efficiency of 58.0% and 33.4%, which were 2.5-fold and 2.0-fold higher than that of the leading commercial gene transfection reagent, Lipofectamine 3000. Excitingly, H-LPAE B4−S5−TMPTA mediated 56.7% and 28.1% cell apoptosis in HepG2 cells and HeLa cells highlighting its potential application in cancer gene therapy. In addition, locally administered H-LPAE B4−S5−TMPTA delivered TRAIL DNA to HepG2 xenograft tumors and inhibited tumor growth in vivo. This study not only proposes a novel strategy for synthesizing poly(β-amino ester)s with a unique branched-linear topology but also identifies a promising candidate for highly efficient TRAIL gene transfection.

研究领域: 癌症研究 · 基因治疗 · 聚合物化学 · 分子生物学
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Materials Science & Engineering C-Materials for Biological Applications · 2018 · IF 5.08

Red fluorescent ZnO nanoparticle grafted with polyglycerol and conjugated RGD peptide as drug delivery vehicles for efficient target cancer therapy

Xiaoxin Yang,Chuang Zhang,Anxia Li,Jie Wang,Xiulan Cai

In the field of modern nanomedicine, ZnO nanoparticles were considered as an emerging candidate for drug delivery because of their inherent biocompatibility and stability. However, the poor dispersibility in a physiological medium obstructed their clinic applications. In this paper, the red fluorescence ZnO nanoparticles were synthesized, using a facile chemical method of polyol in boiling trimethylene glycol (TREG) with zinc acetate. The as-synthesized ZnO nanoparticles were first time grafted with PG layer through ring-opening polymerization of glycidol (ZnO-PG). As calculated from the TGA data, the weight ratio of the grafted PG was about 68 wt%. Then, the ZnO-PG engineered to conjugate with arginine-glycine-aspartate (RGD) peptide by stepwise organic reactions. Finally, anticancer drugs Doxorubicin hydrochloride (DOX) was immobilized on ZnO-PG-RGD (approximately 21.8 ± 0.9 nm) to form ZnO-PG-RGD/DOX. The drug release percentage reaches 70.6% within 48 h under pH 5.2, which was more than 3-fold higher than that pH 7.4. The properties of ZnO nanoparticles and its derivatives were detected by power XRD, TEM, EDS, FTIR, TGA, DLS, Zeta potential and UV. The grafted PG layer not only largely enhanced the dispersibility, but also inhibited ZnO nanoparticles from the uptake by U87MG and Hela cells. In contrast, ZnO-PG-RGD was selectively taken up by U87MG, not Hela cells, demonstrating an obvious targeting property. When ZnO-PG-RGD/DOX was used, U87MG cells showed specificity damaged compared with Hela cells. Thus, functionalized ZnO nanoparticle was a promising nanomaterial in cancer theranostics.

研究领域: 纳米医学 · 药学 · 癌症研究 · 材料科学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2021 · IF 3.205

A terminal alkyne and disulfide functionalized agarose resin specifically enriches azidohomoalanine labeled nascent proteins

Zhanwu Hou,Xiao Han,Zhen Wang,Sana Ghazanfar,Jeffy Yang,Huadong Liu

Nascent proteome presents dynamic changes in response to a certain stimulus. Thus, monitoring nascent proteome is critical to uncovering the involved biological mechanism. But the low-abundance of nascent proteome against an overwhelming pre-existing proteome limits its identification and quantification. Herein, we present a novel strategy to enrich nascent proteome from whole cell lysate for further analysis by mass spectrometry. We employed a terminal alkyne and disulfide functionalized agarose resin to capture nascent proteome which had been labeled by L-azidohomoalanine. Results from the western blot, silver staining and pulse metabolic labeling suggested that the nascent proteome could be enriched efficiently. Applied to Hela cells, the method identified about 700 nascent proteins with good correlation with previous reports. The above indicates that our strategy can be used to reveal the proteome dynamics of biological processes.

CAS / MDL: 106-96-7 56-17-7
研究领域: 蛋白质组学 · 细胞生物学 · 生物化学 · 质谱
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MACROMOLECULAR MATERIALS AND ENGINEERING · 2018 ·Vol. 303 ·期 10 ·1800330 · IF 2.69

Building Micelle Analog Nanoparticle for Multidrug Delivery: Dual-Polymer Nanoparticles with Hydrophilic Shell and Double Hydrophobic Layers

Zhengzhong Wu,Yanjun Liu,Jun Cao,Lei Huang,Xianglin Luo

Multidrug delivery systems are capturing much attention while ingenious drug carriers are drug delivery researchers' pursuit. A method building dual-polymer nanoparticles (DPNs), one analogous micelle nanoparticle, with double hydrophobic core layers and a hydrophilic shell, is developed by combining co-axial injection and solvent evaporation using a hydrophobic and an amphiphilic polymer. Hydrophobic drugs can be efficiently and zonally encapsulated in core and/or outer hydrophobic zone of DPN. As a result, DPN can sequentially release drugs and appears stronger growth inhibition to Hela cells and cell uptake than normal drug-loaded micelles. Moreover, this method is universal to other material combinations of hydrophobic/amphiphilic polymers. Therefore, DPN has potential as one multidrug delivery system.

研究领域: 纳米技术 · 药剂学 · 药物递送系统 · 生物医学工程
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Soft Matter · 2019 ·Vol. 15 ·期 9 ·2051-2056 · IF 3.399

Enantioselective cytotoxicity of chiral polymer vesicles with linear and hyperbranched structures

Funing Liu,Hongli Zhang,Junjie Cheng,Jingang Hu,Chenlu He,Qijin Zhang,Gang Zou

Herein, we study the enantioselective cytotoxicity of vesicles self-assembled by optically active linear polymers (LNPs) and hyperbranched polymers (HBPs). Compared to HBP vesicles, LNP vesicles exhibit properties such as a higher surface charge density and more violent interaction with simulated biomembranes which results in larger cytotoxicity against HeLa cells. Specifically, racemic-LNP vesicles exhibit the largest cytotoxicity of all. More interestingly, there is no significant enantioselective dependence of HBP vesicles on the abovementioned properties. Overall, we proved that the cytotoxicity of vesicles is deeply related to chirality and topological-structures. This research is of great fundamental value for the design of novel bio-interface materials.

CAS / MDL: 109-55-7
研究领域: 材料科学 · 生物医学工程 · 聚合物化学 · 细胞生物学
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MOLECULAR PHARMACEUTICS · 2019 · IF 4.396

Vinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process

Yongyan Zhu,Ruixuan Liu,Haoji Huang,Quanhong Zhu

Molecularly imprinted polymers have exhibited good performance as carriers on drug loading and sustained release. In this paper, vinblastine (VBL)-loaded polymeric nanoparticles (VBL–NPs) were prepared by a one-step molecular imprinting process, avoiding the waste and incomplete removal of the template, and evaluated as targeting carriers for VBL delivery after modification. Using acryloyl amino acid comonomers and disulfide cross-linkers, VBL–NPs were synthesized and then conjugated with poly(ethylene glycol)–folate. The dynamic size of the obtained VBL–NPs–PEG–FA was 258.3 nm (PDI = 0.250), and the encapsulation efficiency was 45.82 ± 1.45%. The nanoparticles of VBL–NPs–PEG–FA were able to completely release VBL during 48 h under a mimic tumor intracellular condition (pH 4.5, 10 mM glutathione (GSH)), displaying significant redox responsiveness, whereas the release rates were much slower in the mimic body liquid (pH 7.4, 2 μM GSH) and tumor extracellular environment (pH 6.5, 2 μM GSH). Furthermore, the carriers NPs–PEG–FA, prepared without VBL, showed satisfactory intrinsic hemocompatibility, cellular compatibility, and tumor-targeting properties: they could rapidly and efficiently accumulate to folate receptor positive Hela cells and then internalized via receptor-mediated endocytosis, and the retention in tumor tissues could last for over 48 h. Interestingly, VBL–NPs–PEG–FA could evidently increase the accumulation of VBL in tumor tissues while decreasing the distribution of VBL in organs, exert similar anticancer efficacy against Hela tumors in the xenograft model of nude mice to VBL injection, and significantly improve the abnormality of liver and spleen observed in VBL injection. VBL–NPs–PEG–FA has the potential to be the delivery carrier for VBL by enhancing the tumor-targeting efficacy of VBL and decreasing toxicity to normal tissues.

CAS / MDL: 67-68-5
研究领域: 药学 · 生物技术 · 纳米技术 · 癌症研究 · 药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

β-Cyclodextrin coated and folic acid conjugated magnetic halloysite nanotubes for targeting and isolating of cancer cells

Xiufang Li,Jian Chen,Hui Liu,Zhiwei Deng,Jianbing Li,Tao Ren,Ling Huang,Wenqing Chen,Yanjing Yang,Shian Zhong

The study developed a simple, effective and inexpensive strategy for capturing, enriching and detecting circulating tumor cells (CTCs) by using folic acid (FA) as the targeting molecule instead of antibodies. This work constructed magnetic halloysite nanotubes (MHNTs) coated with biocompatible β-cyclodextrin (CD), and conjugated to FA via a PEG-Ad linker, to specifically capture the FA receptor (FR)-overexpressing cancer cells. The capture efficiencies of [email protected] β [email protected] for the Skov3, Hela and A549 cancer cells were 96.3%, 97.0% and 95.6% respectively. In addition, the nanoparticles were able to capture very low numbers of the cancer cells (25–500 cells/mL) from PBS and whole blood, as well as selectively capture the cancer cells over normal HEK 293 T cells. Furthermore, the captured cells were viable and grew normally in vitro , indicating the future potential of downstream analyses. This approach can be adapted for different CTCs, once the tumor-specific surface markers are identified and the efficacy of targeting ligands is established. Taken together, FA-conjugated MHNTs nanoparticles are a highly promising tool for isolating CTCs for the diagnosis and treatment of cancer.

研究领域: 纳米技术 · 癌症生物学 · 生物医学工程 · 分子生物学 · 药物递送系统
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JOURNAL OF ETHNOPHARMACOLOGY · 2019 · IF 3.414

Anti-cancer activity of Conyza blinii saponin against cervical carcinoma through MAPK/TGF-β/Nrf2 signaling pathways

Lei Peng,Chenxi Hu,Chaozheng Zhang,Yingying Lu,Shuli Man,Long Ma

Ethnopharmacological relevance Conyza blinii H.Lév. is a type of natural plant distributed in southwest of China. Its dried overground section can be used in traditional Chinese medicine (TCM) for treating infections, inflammations and occasionally cancers. CBS ( Conyza blinii saponin), mainly composed of triterpenoidal saponins of Conyza blinii H.Lév. CBS is considered as the major active fraction of this species. The current investigation have focused on the mechanisms of CBS with regard to its anti-cancer activity. Hence it is of high relevance of identifying the anti-cancer efficacy of ethnomedicine . Aim of the study To understand the anti-cancer mechanism of CBS using both in vitro and in vivo experiments. Materials and methods CBS ( Conyza blinii saponin) was obtained as described previously. We tested the anti-cancer activity of CBS using in vitro HeLa cell models and in vivo animal models. We adopted immunoblot , RT-PCR (reverse transcription polymerase chain reaction), luciferase reporter assay and flow cytometry to study relevant proteins, genes, pathways and cellular ROS (reactive oxygen species) responsible for anti-cancer activity of CBS. More, 24 tumour-xenografted mice were grouped randomly as ‘control’, ‘cisplatin’ (as positive control), ‘low dose’ and ‘high dose’ groups. The IL-1β, TNF-α, PGE2 and IL-2 in the blood serum and the tumour tissue of mice were measured. Results and conclusions We have found that CBS is capable of inducing apoptotic cancer cell death via both caspase-dependent and -independent pathways. CBS inhibits the activation of TGF-β signaling pathway in a dose- and time-dependent manner. Phospho-ERK, phospho-JNK and phospho-p38 MAPK are significantly suppressed by CBS. Furthermore, some inflammation mediators including IL-1β, TNF-α and PGE2 from animal samples were found decreased in CBS-treated mice models. In contrast, the level of IL-2, a cytokine commonly used for treating cancers, increased reversely. Last, we have discovered that CBS is able to decrease the expression of Nrf2, inhibit the activation of ARE and increase ROS level in HeLa cells. In summary, we have confirmed that the anti-cancer activity of CBS is possibly related to its TGF-β, MAPK, Nrf2 signaling pathways as well as some cancer related inflammation mediators and cytokines.

CAS / MDL: 4091-99-0
研究领域: 药理学 · 肿瘤学 · 民族药理学 · 细胞生物学 · 分子生物学
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Arabian Journal of Chemistry · 2023 · IF 6

Endoplasmic reticulum-targetable selenium-doped carbon nanodots with redox-responsive fluorescence for in situ free-radical scavenging in cells and mice

Lei Yang,Hong Huang,Ting Wang,Danling Zhou,Qing Chen,Dan Li,Shuzi Chen,Ping Lin

Endoplasmic reticulum, the largest cellular organelle where protein synthesis, folding, transportation, and the maintenance of Ca 2+ homeostasis occurred, is sensitive to the imbalance of its inner environment. Particularly, overproduction of reactive oxygen species in endoplasmic reticulum region can initiate endoplasmic reticulum stress and is tightly related to many metabolic diseases. In this respect, to retain normal function of endoplasmic reticulum, it is highly important to synthesize antioxidants with endoplasmic reticulum-targeting capability for precisely clearing excessively generated reactive oxygen species in endoplasmic reticulum. Herein, we demonstrate the preparation of endoplasmic reticulum-targeting Se-doped carbon nanodots and assays with HeLa cells as well as in vivo tests with mice have shown that the prepared carbon nanodots can significantly eliminate both •OH and O 2 •− . Experimental results declared that the fabricated carbon nanodots with powerful scavenging capabilities toward •OH and O 2 •- , low cytotoxicity and endoplasmic reticulum targetability can be utilized to protect cells against raised levels of reactive oxygen species in endoplasmic reticulum. What’s more, the fabricated carbon nanodots effectively alleviated phorbol 12-myristate 13-acetate induced ear inflammation in live mice.

研究领域: 纳米技术 · 生物医学工程 · 细胞生物学 · 药理学
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CHINESE JOURNAL OF CHEMICAL PHYSICS · 2020 ·Vol. 33 ·期 3 ·376-384 · IF 1.067

Magnetic nano-amorphous-iron-oxide-based drug delivery system with dual therapeutic mechanisms

Lei Shan,Wang Li-an,Lin Fu-xing,Zeng Kun,Wanga Mo-zhen,Gea Xue-wu

Smart nanoparticles that respond to pathophysiological parameters, such as pH, GSH, and H 2 O 2 , have been developed with the huge and urgent demand for the high-efficient drug delivery systems (DDS) for cancer therapy. Herein, cubic poly(ethylene glycol) (PEG)-modified mesoporous amorphous iron oxide (AFe) nanoparticles (AFe-PEG) have been successfully prepared as pH-stimulated drug carriers, which can combine doxorubicin (DOX) with a high loading capacity of 948 mg/g, forming a novel multifunctional AFe-PEG/DOX nanoparticulate DDS. In an acidic microenvironment, the AFe-PEG/DOX nanoparticles will not only release DOX efficiently, but also release Fe ions to catalyze the transformation of H 2 O 2 to OH, acting as fenton reagents. In vitro experimental results proved that the AFe-PEG/DOX nanoparticles can achieve combination of chemotherapeutic (CTT) and chemodynamic therapeutic (CDT) effects on Hela tumor cells. Furthermore, the intrinsic magnetism of AFe-PEG/DOX makes its cellular internalization efficiency be improved under an external magnetic field. Therefore, this work develops a new and promising magnetically targeted delivery and dual CTT/CDT therapeutic nano-medicine platform based on amorphous iron oxide.

研究领域: 纳米技术 · 药学 · 癌症治疗 · 材料科学
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