查找使用阿拉丁产品的科研文献

Acute and chronic toxicity of tetrabromobisphenol A to three aquatic species under different pH conditions

Qun He,Xinghao Wang,Ping Sun,Zunyao Wang,Liansheng Wang

Tetrabromobisphenol A (TBBPA) is a well-known brominated flame retardant. It has been detected in the environment and shows high acute toxicity to different organisms at high concentrations. In this work, the effects of pH and dimethyl sulfoxide (DMSO) on the acute toxicity of TBBPA to Daphnia magna and Limnodrilus hoffmeisteri were tested, and the oxidative stress induced by TBBPA in livers of Carassius auratus was assessed using four biomarkers. The integrated biomarker response (IBR) was applied to assess the overall antioxidant status in fish livers. Moreover, fish tissues (gills and livers) were also studied histologically. The results showed that low pH and DMSO enhanced the toxicity of TBBPA. Furthermore, changes in the activity of antioxidant enzymes and glutathione level suggested that TBBPA generates oxidative stress in fish livers. The IBR index revealed that fish exposed to 3   mg/L TBBPA experienced more serious oxidative stress than exposed to acidic or alkaline conditions. The histopathological analysis revealed lesions caused by TBBPA. This study provides valuable toxicological information of TBBPA and will facilitate a deeper understanding on its potential toxicity in realistic aquatic environments.

A pH-responsive nanocontainer based on hydrazone-bearing hollow silica nanoparticles for targeted tumor therapy

Liangliang Dai,Qingfeng Zhang,Xinkun Shen,Qiang Sun,Caiyun Mu,Hao Gu,Kaiyong Cai

A pH-responsive drug delivery system based on hollow mesoporous silica nanoparticles (HMSNs) was fabricated for targeted tumor therapy by using hydrazone bonds as pH-sensitive linkers and hyaluronic acid (HA) molecules as both blocking and targeting agents. HMSNs were synthesized with good dispersion and dimensions of around 88 nm. Detailed material characterisation suggested that the drug delivery system was successfully constructed. It displayed a fast pH stimulus response for controlled drug release in vitro. Besides, systematic biological investigations revealed that the drug delivery system had good biocompatibility, which could effectively target tumor cells and deliver therapeutic cargo to induce tumor cell apoptosis in vitro and suppression of tumor growth in vivo. This study reports a promising drug delivery system for potential clinical application against tumor therapy.

pH Responsiveness of Hexosomes and Cubosomes for Combined Delivery of Brucea javanica Oil and Doxorubicin

Yawen Li,Angelina Angelova,Fangzhou Hu,Vasil M. Garamus,Changjun Peng,Na Li,Jianwen Liu,Dan Liu,Aihua Zou

We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by Brucea javanica oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH = 7.4) to cubic (pH = 6.8) to emulsified microemulsion (pH = 5.3) phase transition with a therapeutic application in cancer inhibition. BJO is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an antitumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need for safe delivery carriers. Here, pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein–oleic acid–BJO–DOX) systems are determined by synchrotron small-angle X-ray scattering and the Langmuir film balance technique. The nanocarrier assemblies display good physical stability in the studied pH range and adequate particle sizes and ζ-potentials. Their interaction with model lipid membrane interfaces is enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO–DOX dual-loaded pH-switchable liquid crystalline nanoparticles are performed on the human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines exhibit enhanced antitumor efficacy. The performed preliminary studies suggest a potential reversal of the resistance of the MCF-7/DOX cells to DOX. These results highlight the necessity for further understanding the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, and emulsified microemulsion inner organizations for therapeutic outcomes.

Co-delivery of erlotinib and doxorubicin by pH-sensitive charge conversion nanocarrier for synergistic therapy

Yongju He,Zhigui Su,Lingjing Xue,Hui Xu,Can Zhang

Pretreatment of lung cancer cells with epidermal growth factor receptor (EGFR) inhibitor erlotinib has been recently reported that could dramatically synergize their apoptotic response to DNA damage agent doxorubicin (DOX). To translate this synergistic therapy into in vivo anticancer therapy and clinical practice, we designed a novel pH-sensitive charge conversion nanocarrier (M-HHG 2 C 18 -L) that contained erlotinib/DOX combination and produced a sequential staggered drug release for synergistic lung cancer therapy. In this study, a synthetic zwitterionic oligopeptide lipid (1,5-dioctadecyl- l -glutamyl2-histidyl-hexahydrobenzoic acid, HHG 2 C 18 ) was used to construct a pH-sensitive lipid bilayer (HHG 2 C 18 -L), which was subsequently applied to coat amino-functionalized mesoporous silica nanoparticles (MSN-NH 2 ). Erlotinib and DOX were separately incorporated into HHG 2 C 18 -L and MSN-NH 2 respectively to obtain pH-sensitive charge conversion erlotinib/DOX co-delivery nanoparticles (M-HHG 2 C 18 -L(E   +   D)). We confirmed that M-HHG 2 C 18 -L(E   +   D) were able to reverse surface zeta potential from negative to positive at tumor extracellular pH, thus facilitating the targeted cancer cell internalization. Furthermore, as erlotinib was sequestered in the exterior lipid bilayer and the controlled release ability of MSN-NH 2 , erlotinib released faster than DOX during the cellular transport. Additionally, HHG 2 C 18 -L became more positive at tumor intracellular pH and enhanced Coulombic repulsion with MSN-NH 2 , leading to increased sequential staggered release of erlotinib and DOX. Due to the pretreatment and time-staggered inhibition of EGFR with erlotinib and the enhanced intracellular release of DOX to the nucleus, the maximized synergistic cell killing effect was achieved. Compared to non-sensitive erlotinib/DOX co-delivery nanoparticles (M-SPC-L(E   +   D)) and simultaneous DRUG coadministration. M-HHG 2 C 18 -L(E   +   D) with sequential staggered drug release and pH-sensitive charge conversional properties showed great synergistic effects in antiproliferation and apoptosis of A549 human cancer cells in vitro. The in vivo study demonstrated that M-HHG 2 C 18 -L(E   +   D) exhibited considerable tumor accumulation and potent suppression of tumor growth in Lewis lung carcinoma tumor bearing mice. It was also demonstrated that M-HHG 2 C 18 -L(E   +   D) showed no systemic toxicity and possessed distinguished effect on extending survival period. These results suggested that M-HHG 2 C 18 -L(E   +   D) had great potential application in cancer treatment.

Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy

Zhiqiang Ma,Pengwei Hu,Changyong Guo,Dan Wang,Xingjie Zhang,Min Chen,Qirong Wang,Miao Sun,Peiyu Zeng,Fengkun Lu,Linhong Sun,Lan She,Hongtao Zhang,Jianzhong Yao,Feng Yang

Injectable, NIR/pH-Responsive Nanocomposite Hydrogel as Long-Acting Implant for Chemophotothermal Synergistic Cancer Therapy

Xiaoyu Xu,Ziyuan Huang,Zeqian Huang,Xuefei Zhang,Siyu He,Xiaoqi Sun,Yifeng Shen,Mina Yan,Chunshun Zhao

In this study, gold nanorods (GNRs) were incorporated into the hydrogel networks formed by the copolymerization of N-isopropylacrylamide (NIPAm) and methacrylated poly-β-cyclodextrin (MPCD)-based macromer to fabricate an injectable and near-infrared (NIR)/pH-responsive poly(NIPAm-co-MPCD)/GNRs nanocomposite hydrogel, which could serve as a long-acting implant for chemophotothermal synergistic cancer therapy. The nanocomposite hydrogel showed superior mechanical and swelling properties, gelation characteristics, and excellent NIR-responsive property. A hydrophobic acid-labile adamantane-modified doxorubicin (AD-DOX) prodrug was loaded into the hydrogel efficiently by host–guest interaction. The nanocomposite hydrogel exhibited a manner of sustained drug release and could sustain the slow and steady release of DOX for more than 1 month. The pH-responsive release of DOX from the nanocomposite hydrogel was observed owing to the cleavage of acid-labile hydrazone bond between DOX and the adamantyl group in acidic environment. NIR irradiation could accelerate the release of DOX from the networks, which was controlled by the collapse of the hydrogel networks induced by photothermal effect of GNRs. The in vitro cytotoxicity test demonstrated the excellent biocompatibility and photothermal effect of the nanocomposite hydrogel. Moreover, the in situ-forming hydrogel showed promising tissue biocompatibility in the mouse model study. The in vivo antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemophotothermal synergistic therapy with reduced adverse effects owing to the prolonged drug retention in the tumor region and efficient photothermal effect. Therefore, this injectable and NIR/pH-responsive nanocomposite hydrogel exhibited great potential as a long term drug delivery platform for chemophotothermal synergistic cancer therapy.

Sensitive and precise visually guided drug delivery nanoplatform with dual activation of pH and light

Chenyu Liu,Hengjun Zhou,Simiao Yu,Hailiang Chen,Ning Wang,Weihe Yao,An-Hui Lu,Weihong Qiao

Controlled-release drug carriers in cancer therapy are the most ideal way to reduce toxicity and improve drug efficacy . Since light stimulation is precise and operable, most multi-stimulation response carriers utilize phototherapy to enhance release efficiency. However, phototoxicity severely limits the application of phototherapy. Herein, we designed and synthesized a Cou-ONB lipid with sensitive fluorescence feedback and multi-stimulus response. COBL liposomes prepared from Cou-ONB lipids will passively aggregate at the tumor and guide phototherapy by fluorescence. More importantly, it can reflect the drug release effect in vivo through its own sensitive fluorescence changes, further enabling precise phototherapy and reducing phototoxicity. In this paper, the multi-stimulus superimposed response and precise fluorescence-guided performance of COBL liposomes were investigated at the molecular, liposome, cellular, and animal levels. Finally, tumor treatment experiments showed that the d -COBL-UV group had the best tumor suppression effect (5.3-fold). This paper highlights a real-time fluorescence-guided multi-stimulus superposition strategy and provides a design idea to precisely implement exogenous stimuli by displaying the degree of drug release, aiming to achieve less toxic and more efficient cancer therapy through timely and precise multi-stimulation. Statement of significance Multi-stimulus responsive drug carriers have been extensively developed in the last decade. Visual guidance is an important tool to achieve precision medicine and precise control of drug release. However, the available visualization materials are more aimed at directing stimulation at the optimal moment. There is little discussion on when to stop exogenous stimulation and how to minimize the damage of stimulation to the patient. Here, we provide a Cou-ONB lipid that not only responds to multiple stimuli, but also provides sensitive feedback on its own dissociation with a fluorescent signal so that physicians can adjust exogenous stimuli in a timely manner. This paper provides insights to facilitate precision drug delivery systems, providing viable design ideas for precise, efficient, and less toxic cancer therapies.

PVDF ultrafiltration membrane with enhanced mechanical and filtration performance by hydrophilic pH-response nanofibers modification

Hengyang Mao,Shouyong Zhou,Meisheng Li,Rong Wang,Zhong Ma,Huifang Xiao,Ailian Xue,Yijiang Zhao,Wenbo Peng,Chenglung Chen

Membrane separation is an efficient strategy to disrupt the spread of pathogens in an aqueous solution and produce clean water, but its performance is seriously affected by fouling caused by bioadhesive. In this study, novel pH-response attapulgite (p-ATP) nanofibers were prepared and applied in the modification of poly(vinylidene fluoride) (PVDF) ultrafiltration membrane for bovine serum albumin (BSA) solution purification. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) was grafted onto the surface of attapulgite (ATP) to offer pH-response property and to improve compatibility with PVDF. p-ATP is a hydrophilic material, which can increase the anti-biofouling performance of PVDF, and its one-dimensional structure is beneficial for enhancing the inter-entanglement with organic chains in the membrane matrix. The resultant composite membrane loaded with 7% p-ATP presented 77.2% and 108.1% increase in stationary permeance and mechanical strength, respectively, than that of the pristine PVDF membrane. Furthermore, the PDMAEMA chains in p-ATP will be shrunken or swollen with the change of pH value, resulting in adsorbing or releasing water molecules. This process is effective to mitigate the adhesion between biofoulants and membrane and can break the already formed biofouling layer. So, the composite membranes are easily to be cleaned via a simple pH-change cleaning process. The molecular dynamic simulation was also conducted to analyze the high performance of the PVDF/p-ATP membrane to provide theoretical support.

Triazolone/alginate-zinc (II)-montmorillonite sustained release system with improved adsorption capacity and pH-sensitivity

Chen Huayao,Zhan Jinghui,Zhou Hongjun,Hao Li,Xu Hua,Pu Xia,Zhou Xinhua

Developing effective sustained release system is an efficient way to prevent the pollution from overused pesticide. Hence, a highly efficient sustained release system was developed using zinc (II) modified montmorillonite (Zn–Mt) prepared by ion exchange from sodium montmorillonite (Na–Mt) with zinc nitrate. Zn–Mt was modified by sodium alginate (ALG) to further improve its sustained release performance and pH-sensitivity. The results indicated that triazolone was supported on the zinc modified montmorillonite through the coordination bond from zinc ion. The zinc ion in the Mt also played a similar role as calcium ion to induce ALG crosslinking which made ALG highly dispersed in the pores of Mt. ALG interacted with Zn 2+ from Mt through electrostatic interaction and winded with triazolone to form a barrier for the sustained release system. As a result, the adsorption capacity of ALG–Zn–Mt (17.75 mg/g) was improved comparing with Na–Mt without modification (14.52 mg/g). The sustained release performance of ALG–Zn–Mt showed also significant pH-sensitivity in accordance with the stability of ALG.

Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

Yang Liu,Juan Li,Zhi Li,Xing Tang,Zhenzhong Zhang

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

Development of oral curcumin based on pH-responsive transmembrane peptide-cyclodextrin derivative nanoparticles for hepatoma

Tiantian Wei,Yin Zhang,Meng Lei,Yanru Qin,Zhongjie Wang,Zhimeng Chen,Liefeng Zhang,Yongqiang Zhu

Herein, a pH-responsive cyclodextrin derivative (R6H4-CMβCD) with cell-penetrating ability was successfully synthesized, and curcumin-loaded nanoparticles (R6H4-CMβ [email protected] NPs, RCCNPs) were developed to improve its efficacy in hepatoma. RCCNPs could improve the cell uptake compared with CMβ [email protected] NPs (CCNPs) and were internalized into cells mainly through endocytosis mediated by reticulin and macropinocytosis . Furthermore, the accumulation of RCCNPs in hepatoma cells at pH 6.4 was higher than that at pH 7.4, indicating a pH-responsive uptake. Additionally, RCCNPs could escape from the lysosomes via the “proton sponge effect”, and a high apoptosis rate was detected. Importantly, in vivo experiments revealed that orally administered RCCNPs could exert excellent anti-cancer effects in tumor-bearing mice. Hematoxylin-eosin staining did not show significant histological changes in the major organs. Thus, our findings indicate the potential of R6H4-CMβCD as a nanopharmaceutical material, and RCCNPs as an effective delivery system for oral curcumin in cancer management.

Protocol for Proximity-Dependent Proteomic Profiling in Yeast Cells by APEX and Alk-Ph Probe

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) .