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JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY · 2014 ·Vol. 72 ·期 1 ·106-113 · IF 1.547

A novel pH-responsive controlled release system based on mesoporous silica coated with hydroxyapatite

Cui Liru,Lin Huiming,Guo Wei,Xiang Di,Zhou Dan,Zhang Ting,Qu Fengyu

With well bioactive and nontoxic, hydroxyapatite (HAp) was employed to seal the nanopores of mesoporous silica (MCM-41) to realize the pH-responsive controlled release. First, MCM-41 was modified with cationic polymer, poly-(diallyldimethylammoniumchloride) (PA). And after the addition of Ca 2+ /PO 4 3− , HAp precipitation can take place based on the cationic sites derived from PA. It is a simple and effective way to obtain HAp coating MCM-41 system (MHAs). The structure of the system was characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, N 2 adsorption–desorption and so on. Metformin hydrochloride was used as the model drug, and the drug release performance and the release kinetics of the system were investigated in detail. Because of the degradation of HAp under acid condition, the drug loading MHAs showed a well pH-sensitive controlled release behavior. From above investigation, MHAs is a promising platform to construct a pH-responsive controlled drug delivery system, especially for some low pH tissues, such as inflammatory and tumor.

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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2016 ·Vol. 409 ·期 5 ·1387-1394 · IF 3.125

Biological pH sensing based on the environmentally friendly Raman technique through a polyaniline probe

Li Songyang,Liu Zhiming,Su Chengkang,Chen Haolin,Fei Xixi,Guo Zhouyi

The biological pH plays an important role in various cellular processes. In this work, a novel strategy is reported for biological pH sensing by using Raman spectroscopy and polyaniline nanoparticles (PANI NPs) as the pH-sensitive Raman probe. It is found that the Raman spectrum of PANI NPs is strongly dependent on the pH value. The intensities of Raman spectral bands at 1225 and 1454 cm −1 increase obviously with pH value varying from 5.5 to 8.0, which covers the range of regular biological pH variation. The pH-dependent Raman performance of PANI NPs, as well as their robust Raman signals and sensitivities to pH, was well retained after the nanoparticles incorporated into living 4T1 breast adenocarcinoma cells. The data indicate that such PANI NPs can be used as an effective biological pH sensor. Most interestingly, the PANI spherical nanostructures can be acquired by a low-cost, metal-free, and one-pot oxidative polymerization, which gives them excellent biocompatibility for further biological applications.

✓ 已验证 DOI PubMed 高影响因子
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ANALYST · 2018 ·Vol. 143 ·期 20 ·5054-5060 · IF 3.864

A naphthalene-based fluorescent probe with a large Stokes shift for mitochondrial pH imaging

Bo Lin,Li Fan,Jinyin Ge,Wenjia Zhang,Caihong Zhang,Chuan Dong,Shaomin Shuang

A mitochondrial-targeted pH fluorescent probe 4-(2-(6-hydroxynaphthalen-2-yl)vinyl)-1-methylpyridin-1-ium was facilely synthesized via the carbon–carbon double bond bridging of 6-hydroxy-2-naphthaldehyde and 1,4-dimethylpyridinium iodide salt. The probe exhibited remarkable pH-dependent behavior in the linear range of 7.60–10.00, with a pKa value of 8.85 ± 0.04 near mitochondrial pH. A significantly large Stokes shift of 196 nm was obtained, which reduces the interference of excitation light. Application of the probe in live HepG2 cells indicated that the probe had excellent mitochondrial targeting ability and was successfully used to visualize mitochondrial pH fluctuations in live cells.

✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2017 · IF 3.887

NGR-modified pH-sensitive liposomes for controlled release and tumor target delivery of docetaxel

Zili Gu,Minglu Chang,Yang Fan,Yanbin Shi,Guimei Lin

As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200   nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment.

✓ 已验证 DOI PubMed 高影响因子
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Acta Biomaterialia · 2015 · IF 6.025

Enhanced antitumor efficacy by cyclic RGDyK-conjugated and paclitaxel-loaded pH-responsive polymeric micelles

Yajie Gao,Yanxia Zhou,Lei Zhao,Chao Zhang,Yushu Li,Jinwen Li,Xinru Li,Yan Liu

Cyclic RGDyK (cRGDyK)-conjugated pH-sensitive polymeric micelles were fabricated for targeted delivery of paclitaxel to prostate cancer cells based on pH-sensitive copolymer poly(2-ethyl-2-oxazoline)-poly( d , l -lactide) (PEOz-PLA) and cRGDyK-PEOz-PLA to enhance antitumor efficacy. The prepared micelles with an average diameter of about 28   nm exhibited rapid release behavior at endo/lysosome pH, effectively enhanced the cytotoxicity of paclitaxel to PC-3 cells by increasing the cellular uptake, which was correlated with integrin α v β 3 expression in tumor cells. The active targeting activity of the micelles was further confirmed by in vivo real time near-infrared fluorescence imaging in PC-3 tumor-bearing nude mice . Moreover, the active targeting and pH-sensitivity endowed cRGDyK-conjugated micelles with a higher antitumor effect in PC-3 xenograft-bearing nude mice compared with unmodified micelles and Taxol with negligible systemic toxicity. Therefore, these results suggested that cRGDyK-conjugated pH-sensitive polymeric micelles may be a promising delivery system for efficient delivery of anticancer drugs to treat integrin α v β 3 -rich prostate cancers.

✓ 已验证 DOI PubMed 高影响因子
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Journal of Science-Advanced Materials and Devices · 2022 · IF 7.382

An investigation of IRMOF-16 as a pH-responsive drug delivery carrier of curcumin

Mengru Cai,Boran Ni,Xueling Hu,Kaixin Wang,Dongge Yin,Gongsen Chen,Tingting Fu,Rongyue Zhu,Xiaoxv Dong,Changhai Qu,Xingbin Yin

Metal–organic frameworks (MOFs) with tunable structures, high porosity, and abundant active sites are considered to be promising drug delivery systems (DDSs). In this study, novel MOFs-based nanoparticles ( [email protected] ) were successfully prepared using Zn-based IRMOF-16 as a carrier and curcumin (CUR) as the model drug. This nanocargo delivery platform has dual capabilities, enabling simultaneous drug delivery and fluorescence imaging. In vitro release experiments showed that nanoparticles were released more quickly under mildly acidic conditions, which proved their potential for tumor microenvironment-responsive drug release. Through in vitro cell experiments, it was found that the nano-drug platform had high antitumor cytotoxicity, which may be related to the mechanism of increasing intracellular reactive oxygen species (ROS), reducing intracellular mitochondrial membrane potential (MMP), and inducing apoptosis. In addition, confocal laser microscopy showed that [email protected] could localize to the nucleus to exert an antitumor effect. Meanwhile, [email protected] exhibited superior antitumor activity compared with pure CUR in vitro experiments. The biocompatibility test of IRMOF-16 showed reasonable biosafety, and no evidence of obvious toxicity was observed in vitro. [email protected] has unique advantages with regard to pH response, biocompatibility, and antitumor efficacy, indicating that the nano-drug platform is a promising drug delivery carrier with an antitumor effect.

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PHARMACEUTICAL RESEARCH · 2020 ·Vol. 37 ·期 7 ·1-13 · IF 3.242

Dual-pH Sensitive Charge-Reversal Drug Delivery System for Highly Precise and Penetrative Chemotherapy

Chen Weiguo,Li Ji,Xing Yan,Wang Xiaowei,Zhang Hongyan,Xia Mingyu,Wang Dongkai

Purpose The complex physiological barriers impose extremely conflicting demands on systemic drug delivery, so both particle size and surface charge of the nanoplatforms become vital factors. As a carbon-based nanomaterial with excellent optical properties, carbon dots are not suitable for direct systemic transport in vivo , which limits their application in the field of biomedical imaging, especially in the areas of diagnosis and cancer treatment. Liposomes have been developed as universal nanocarriers for various drugs. In this study, we aimed to build a highly precise and penetrative drug delivery system (DDS) using carbon dots encapsulated by liposomes. Methods Carbon dots (CDs) were synthesized by the hydrothermal method using citric acid and ethylenediamine. Furthermore, simian virus 40 large T-antigen derived the nuclear targeting sequence (NLS) was bonded on the surface of CDs to obtain CDs-NLS. The antitumor drug doxorubicin was loaded onto the CDs-NLS through an acid-labile hydrazine bond to obtain DOX@CDs. Finally, DOX@CDs were encapsulated in aqueous centers of folate-coated and pH-sensitive liposomes, named pHSL-FA. Results In this paper, a nucleus-targeted nanocomposite (DOX@CDs), which bonds with the nuclear targeting sequence (NLS) and the anticancer drug doxorubicin (DOX), has physicochemical properties of particle size of about 3.8 nm, zeta potential of +31.8 mV and high quantum yield of 64.53%. The negatively charged folate-coated and pH-sensitive liposomes (pHSL-FA) are used as a carrier to reverse the surface charge of DOX@CDs. Compared to free DOX@CDs, pHSL-FA show higher tumor accumulation in 4 T1 tumor-bearing mice and further improve cytotoxicity to tumor cells. Conclusions This work proposes a unique nanomedical approach that enables the precise delivery of chemotherapy drugs and significantly reduces side effects, which is promising for clinical translation.

✓ 已验证 DOI PubMed 高影响因子
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2019 · IF 2.931

Hemicyanine based naked-eye ratiometric fluorescent probe for monitoring lysosomal pH and its application

Yingying Zhang,Yanliang Zhao,Yingnan Wu,Bing Zhao,Liyan Wang,Bo Song

Lysosome as the typical acidic organelle involved in many biological processes, the dysfunction of its pH would alter many diseases. Small-molecule fluorescent probe has been considered as vital tool for monitoring pH fluctuation in living cells. Herein, a hemicyanine based ratiometric fluorescent probe was synthesized, namely, 2,3-trimethy-3-[2-(dimethyl-amino-4-yl) vinyl]-3 H -benzo[ e ]indole ( BiDL ), for rapidly detection pH under acidic conditions. BiDL exhibited ratio fluorescence emission ( F 534nm / F 622nm ) characteristic with p K a 4.25. BiDL showed good linearly response in pH 3.4–4.82, indicating that the probe can be used for quantitative detection pH. The probe also displayed large Stokes shift (112 nm/201 nm) under neutral and acidic conditions, respectively, which could effectively reduce the excitation interference. BiDL had excellent cell membrane permeability , good photo-stability and low toxicity in living cells. The dual-channel confocal fluorescent microscopic ratiometric imaging application of pH in HeLa cells and lysosome were achieved successfully, indicating that BiDL has good potential for investigating lysosome-relevant pathological and physiological processes.

✓ 已验证 DOI PubMed 高影响因子
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EUROPEAN POLYMER JOURNAL · 2015 · IF 3.005

Zwitterionic polymeric micelles that undergo a pH-triggered positive charge for enhanced cellular uptake

Jiawei Lu,Huiyan Jia,Leijia Guo,Genghui Zhang,Youjia Cao,Husheng Yan,Keliang Liu

To achieve a good stealth property and to enhance the uptake by tumor cells, polymeric micelles containing a slightly negatively charged and zwitterionic corona at pH 7.4 (i.e., blood pH) and a positively charged surface at a slightly acidic pH (i.e., tumor extracellular pH) were prepared. The amphiphilic diblock copolymer which was used to prepare the polymeric micelles contains a hydrophilic block comprised of nonionic hydrophilic groups, negatively charged groups (carboxyl groups) and pH-triggered positive charge-generation groups (morpholino groups). The zeta potential of the micelles was found to increase as the pH decreased over the pH range covering the blood and tumor tissue pH ranges, and the corona of the micelles should contain zwitterionic groups. This could be due to that, in the pH range studied, more morpholino groups become protonated as the pH decreased, whereas the carboxyl groups were almost completely deprotonated to form carboxylate anions. Furthermore, by adjusting the molar ratio of morpholino to carboxyl groups, the zeta potential of the polymeric micelles was controlled to achieve a slightly negative value at pH 7.4. Thus, the combination of a slightly negatively charged surface and a zwitterionic corona suggests that these micelles would possess good stealth property. When the pH decreased from 7.4 to 6.8 or 6.5, the zeta potential value of the micelles became positive due to increased protonation of the morpholino groups. Correspondingly, the cellular uptake of the micelles by HeLa cells was enhanced.

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SEPARATION AND PURIFICATION TECHNOLOGY · 2017 · IF 3.359

Chelating extraction of vanadium(V) from low pH sulfuric acid solution by Mextral 973H

Ying Zhang,Ting-An Zhang,David Dreisinger,Weihua Zhou,Feng Xie,Guozhi Lv,Weiguang Zhang

In the current study, a novel chelating extractant Mextral 973H was employed to selectively extract V(V) from a low pH sulfuric acid solution containing high concentration of Fe (Ш). The extraction of V(V) is strongly dependent on solution pH, and the separation coefficient (β (V/Fe) ) between V(V) and Fe(Ш) can be greater than 720 when the solution pH < 0.5. A cation exchange between H and VO 2 + was proposed as the main extraction mechanism at pH < 1.5, while at pH > 1.5, a solvating reaction between the extractant and metal-oxo cluster anions took place. The effects of solution pH, acid medium types, contacting time and temperatures on the extraction and separation of V have been discussed. FT-IR and 1 HNMR were applied to confirm the extraction mechanism and also the degradation behavior of Mextral 973H in some extreme conditions. The loaded vanadium was effectively stripped using a diluted 0.2   M Na 2 CO 3 solution and a total stripping extent of 97% was achieved. The extraction process by Mextral 973H was finally simulated using Aspen Plus simulator comparing to traditional process, the results obtained were in good recovery efficiency and with the advantage of acid and alkali saving.

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Journal of Materials Chemistry B · 2016 ·Vol. 4 ·期 44 ·7130-7137 · IF 4.872

Green preparation of carbon dots for intracellular pH sensing and multicolor live cell imaging

Wen-Jing Wang,Jun-Mei Xia,Ji Feng,Meng-Qi He,Ming-Li Chen,Jian-Hua Wang

Carbon dots are prepared using a green hydrothermal approach with dehydrated shiitake mushroom as the sole carbon source without any additives (these carbon dots are shortly termed as MCDs). Carbonization, surface functionalization and nitrogen doping are involved in the hydrothermal treatment and no further modification or surface passivation is necessary. The derived MCDs are nitrogen-doped, oxygen-rich with hydroxyl, carboxyl and amine groups, with a diameter of ca. 4.2 nm. MCDs exhibit cell permeable properties and a distinct pH-sensitive/excitation-dependent photoluminescence emission feature within pH 4.0–8.0, providing an optical probe for intracellular pH sensing and multicolor imaging of live HeLa cells. MCDs also show a strong fluorescence response to hemin, which facilitates sensitive fluorescent sensing of hemin with a detection limit of 120 nmol L−1.

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ACS Applied Bio Materials · 2020 · IF 0

Engineering a pH/Glutathione-Responsive Tea Polyphenol Nanodevice as an Apoptosis/Ferroptosis-Inducing Agent

Min Mu,Yuelong Wang,Shasha Zhao,Xiaoling Li,Rangrang Fan,Lan Mei,Min Wu,Bingwen Zou,Na Zhao,Bo Han,Gang Guo

Chemotherapy works against tumors by inducing cell apoptosis; however, evasion of apoptosis is recognized to result in resistance to anticancer therapy. Ferroptosis is an iron-dependent cell death pathway that differs from apoptosis in morphological, biochemical, and genetic levels. Combined ferroptosis and apoptosis may shed light on strategies for cancer treatment. Therefore, we have designed a nanoparticle (NP) that can simultaneously cause tumor cell apoptosis and ferroptosis. This NP is composed of epigallocatechin gallate (EGCG) and Fe3+ through a simple and green process and can be used to deliver doxorubicin hydrochloride (DOX) and iron ions to the tumor site at the same time. DOX/Fe3+/EGCG (DF) NPs display a great resolubility and long-term storage stability, and efficient DOX and Fe3+ release is realized after cellular internalization under the high level of glutathione and acidic nature in tumor. EGCG is likely to chemically reduce the released Fe3+ to Fe2+. The generated Fe3+/Fe2+ converts intracellular H2O2 to hydroxyl radicals (•OH) via the Fenton reaction. In addition, the generated •OH subsequently induces lethal ferroptosis to improve DOX-induced apoptosis. In vitro and in vivo investigations indicate that a great therapeutic effect was achieved, suggesting that the formation of the DF NP delivery system is a promising strategy to fight against tumors by an apoptosis and ferroptosis combination modality.

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