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RSC Advances · 2017 ·Vol. 7 ·期 30 ·18270-18276 · IF 3.108

In situ formation of pH-responsive Prussian blue for photoacoustic imaging and photothermal therapy of cancer

Ming Cheng,Wei Peng,Peng Hua,Zhengrong Chen,Jia Sheng,Juan Yang,Yongyou Wu

Designing theranostic agents that are responsive to weakly acidic tumor microenvironments for optimized imaging and therapeutic effects is of great interest in nanomedicine. In the current study, we constructed a pH-triggered smart theranostic system based on pH-responsive Prussian blue, which shows good performance in the photoacoustic imaging (PAI)-guided photothermal therapy (PTT) of tumors. Precursors to Prussian blue, namely ferrous and ferricyanide ions, were separately encapsulated into pH-responsive hydrogels that only degraded under acidic conditions. In vitro results showed that the encapsulated ions were gradually released in acidic buffer, accompanied by hydrogel degradation. After the resultant hydrogel was mixed and intratumorally injected into tumor-bearing mice, the encapsulated ferrous ions and ferricyanide ions were successfully released in the acidic tumor environment, allowing the in situ formation of Prussian blue in the tumor area. This provided an efficient theranostic agent for PAI-guided PTT of cancer. Our research highlights the potential of Prussian blue-based theranostic agents for the precise diagnosis and treatment of cancer.

CAS / MDL: 13746-66-2 7720-78-7
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JOURNAL OF MOLECULAR LIQUIDS · 2016 · IF 2.74

Wormlike micelles with pH-induced rheological property formed by cationic surfactant/anthranilic acid mixed aqueous solution

Wei Lin,Zhengming Yang,Juan Wang,Ting Chen,Xingwang Shi

The pH-induced rheological property of octadecy trimethyl ammonium bromide with anthranilic acid was investigated. The viscoelasticity property and structural transformation of molecular self-assembly were comprehensively discussed by means of rheological measurements, dynamic light scattering and cryogenic-transmission electron microscopy. On the basis of surface tension results, the change of viscoelasticity was explained by calculating the packing parameter of P . UV–vis results confirmed that the pH-dependent interaction between the aromatic ring of anthranilic acid and the head group result in the transition between WLMs and spherical micelles, thus altering the viscoelasticity of WLMs.

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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Highly water-soluble, pH sensitive and biocompatible PAMAM ‘dendrizyme’ to maintain catalytic activity in complex medium

Longgang Wang,Yanshuai Cui,Shengfu Chen,Guangzhi Wang,Dawei Gao,Yanping Liu,Qiaoyue Luo,Zhiwei Liu,Xuwu Zhang

The dendrimer based synthetic mimetic enzyme has been drawing great attention. However, this mimetic enzyme is different from the natural enzymes, which are pH sensitive, biocompatible and keep their catalytic activity in biological complex medium. A single zwitterionic layer composed by primary amine and carboxyl groups may be a useful method to obtain these properties. Herein, we report a novel facile method to prepare a mimetic enzyme. The complexes of generation 5 poly(amido amine) dendrimers (G5 PAMAM) with free hemin (G5Hs) were modified by the maleic anhydride and cysteamine. Results showed that the mimetic enzymes (G5HMCs) had pH sensitivity and good stability by varying the pH from 4 to 9, while significant precipitation was observed for free hemin at pH   5 after two days. The G5HMC (3:1) showed optimal catalytic activity at its isoelectric point. Furthermore, G5HMCs displayed excellent biocompatibility. The G5HMCs incubated with fibrinogen were stable for 24   h, while G5Hs immediately formed large aggregates. G5HMC (3:1 2   mg/mL) displayed little cytotoxicity with HeLa cells or A549 cells for 24   h, while G5H (3:1) had serious cytotoxicity, which was also demonstrated by cell morphology observation. At last, G5HMCs fully preserved their catalytic activity in bovine serum albumin (BSA) solution compared with phosphate buffer saline (PBS) solution, while hemin decreased to 73.5–81.5% catalytic activity in BSA solution, which was caused by the less interaction with BSA for G5HMCs than free hemin. The surface functionalization schemes described in this report would represent a versatile method to prepare water-soluble, pH sensitive, biocompatible, and efficient artificial enzymes for biomedical related applications.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2017 · IF 3.887

pH dependent silver nanoparticles releasing titanium implant: A novel therapeutic approach to control peri-implant infection

Yiwen Dong,Hui Ye,Yi Liu,Lihua Xu,Zuosu Wu,Xiaohui Hu,Jianfeng Ma,Janak L. Pathak,Jinsong Liu,Gang Wu

Peri-implant infection control is crucial for implant fixation and durability. Antimicrobial administration approaches to control peri-implant infection are far from satisfactory. During bacterial infection, pH level around the peri-implant surface decreases as low as pH 5.5. This change of pH can be used as a switch to control antimicrobial drug release from the implant surface. Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for peri-implant infection control. The nanotube arrays were fabricated on the surface of titanium implant as containers; AgNPs were grafted on TNT implant surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR as well as XPS data showed that AgNPs have been successfully linked to TNT via acetal linker without affecting the physicochemical characteristics of TNT. The pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4. AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram-positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT-AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not affect osteoblast morphology in vitro . In conclusion, incorporation of AgNPs in TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs implant was biocompatible to osteoblasts and showed osteoinductive properties. AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this release showed strong antimicrobial properties in vitro . Therefore, this novel design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection-triggered antimicrobial releasing implant model to control peri-implant infection.

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RSC Advances · 2016 ·Vol. 6 ·期 107 ·105957-105968 · IF 3.289

Construction of novel pH-sensitive hybrid micelles for enhanced extracellular stability and rapid intracellular drug release

Shaoping Yin,Liang Chang,Tie Li,Guangji Wang,Xiaochen Gu,Juan Li

It is still a major challenge for successful cancer chemotherapy to design drug delivery systems with desirable extracellular stability and intracellular drug release. Here, novel pH-sensitive hybrid micelles were constructed by introducing positively charged arginine (Arg) into negatively charged micelles formed from a ternary graft copolymer (mPAL) comprising poly(acrylic acid) (PAA) as the backbone and methoxy poly(ethylene-glycol) (mPEG) and poly(lactide) (PLA) as the grafts to balance the extracellular stability and intracellular drug release. Paclitaxel (PTX) loaded hybrid micelles (PTX@mPAL/Arg) exhibited a desirable particle size (62.8 ± 2.9 nm), and a high entrapment efficiency (93.3 ± 2.9%). AFM and TEM images demonstrated the smooth surface and distinct spherical shape of the micelles. PTX@mPAL/Arg displayed high stability against dilution and serum, impeded drug release at physical conditions, and accelerated PTX release in mildly acidic medium. Blank micelles possessed satisfactory compatibility and would be safe for biomedical applications. PTX@mPAL/Arg micelles demonstrated much higher antitumor activity with low IC50 values of 0.67 and 0.20 μg mL−1 for A549 and HepG2 cells following 48 h incubation, respectively. A cellular internalization experiment indicated that the micelles could deliver and release cargo into the cytoplasm of HepG2 cells. Pharmacokinetic study in rats proved that PTX loaded micelles enhanced the AUC of PTX and prolonged circulation time in comparison to Taxol. These intelligent micelles with improved stability and drug release could be further studied as a promising delivery carrier for anticancer agents to improve therapeutic efficacy and to minimize adverse effects.

CAS / MDL: 74-79-3
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International Journal of Nanomedicine · 2024 · IF 6.6

Design and Application of pH-Responsive Liposomes for Site-Specific Delivery of Cytotoxin from Cobra Venom

Qing Lin,Yafei Jing,Cailing Yan,Xinyi Chen,Qiong Zhang,Xinhua Lin,Yunlu Xu,Bing Chen

Background Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.Methods We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.Results CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78±1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78±5.93%).Conclusion Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.

CAS / MDL: 57-88-5 8002-43-5
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JOURNAL OF PHARMACEUTICAL SCIENCES · 2017 · IF 2.713

Dehydroascorbic Acid and pGPMA Dual Modified pH-Sensitive Polymeric Micelles for Target Treatment of Liver Cancer

Haojun Ma,Chen Jiang

In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as lack of potency of tumor penetration. In this work, we developed actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier for HCC therapy. These micelles comprised biodegradable poly(ethylene glycol)-poly(aspartate) polymers, in which paclitaxel can be covalently conjugated to pAsp via an acid-labile acetal bond to form pH-responsive structures. In vitro drug release studies showed that these structures were stable in physiological condition, whereas collapsed once internalized into cells due to the mildly acidic environment in endo/lysosomes, resulting in facilitated intracellular paclitaxel release. In addition, dehydroascorbic acid and guanidinopropyl methacrylamide polymers were decorated on the surface of micelles to achieve specific tumor accumulation and tumor penetration. Cellular uptake and in vivo imaging studies proved that these micelles had remarkable targeting property toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the micelles was also confirmed both in vitro and in vivo . Therefore, this micellar system may be a potential platform of chemotherapeutics delivery for HCC therapy.

CAS / MDL: 929-37-3 106-96-7
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Formation of pH-responsive hydrogel beads and their gel properties: Soybean protein nanofibers and sodium alginate

Yuxin Wang,Xiaoyu Yang,Liang Li

Hydrogel beads prepared from protein nanofibers are popular because of their safety, sleek appearance, and protection of biologically active substances. However, extreme external environmental variations, such as pH and temperature, can limit their practical application. To meet the application requirements of hydrogel beads in different environments, non-covalent mixtures of CaCl 2 cross-linked soybean protein nanofibers (SNF) and sodium alginate (SA) were used to prepare hydrogel beads. In the present study, the hardness (782.48 g) and elasticity of hydrogel beads formed at SNF/SA = 7:3 and CaCl 2 concentration of 0.1 mol/L were the maximum. Furthermore, the water content and pH swelling also reached a peak (98.68 %, 43.85 g/g) due to the best morphology and regular internal network structure. Meanwhile, the pH-responsive hydrogel beads with added anthocyanins were able to respond to the ambient pH under different temperatures and pH conditions and maintained color stability during 96 h of storage (ΔE < 5). In this experiment, a pH-responsive hydrogel bead based on soybean protein nanofiber (SNF) and sodium alginate (SA) was prepared by simple ionic crosslinking. It provides a theoretical and experimental basis for the future application of plant protein nanofibers as pH-responsive hydrogel materials.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes

Zhenjiang Zheng,Mengfei Li,Jianchen Yang,Xintao Zhou,Yonghua Chen,Epiphane K. Silli,Jiali Tang,Songlin Gong,Yuan Yuan,Yihao Zong,Jianping Kong,Pu Chen,Lingxi Yu,Shujun Luo,Ying Wang,Chunlu Tan

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of −19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.

CAS / MDL: 57-88-5
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release

Wenhui Chen,Jiayao Wang,Chiyin Zhang,Shaokui Cao,Jingguo Li,Jun Shi

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

CAS / MDL: 25704-18-1 71550-12-4
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Highly Dispersed Ru-Pt Heterogeneous Nanoparticles on Reduced Graphene Oxide for Efficient pH-Universal Hydrogen Evolution

Junge Yang,Jinxian Feng,Youpeng Cao,Yuxuan Xiao,Lulu Qiao,Keyu An,Jiao Yang,Jing Peng,Hui Pan,Hui-Ming Cheng

An efficient and stable electrocatalyst is key for the production of green hydrogen using water electrolysis. However, the weak dissociation ability of Pt-based catalysts, resulting in slow kinetics severely hampers its applications in alkali medium. Herein, a simple “coincident reduction” strategy is reported to grow highly dispersed Ru-Pt heterogeneous bimetallic nanoparticles on reduced graphene oxide (Ru x Pt y @rGO) for efficient pH-universal hydrogen evolution. Ru x Pt y @rGO has superior catalytic activity at all pH values due to the synergistic effect between Ru and Pt and the ultra-small nanoparticle. In particular, the catalyst with 13.6 wt% of noble metal (Ru 1 Pt 2 @rGO) has low overpotentials of 9, 6, and 36 mV at 10 mA cm −2 in 1 m KOH, 0.5 m H 2 SO 4 and 1 m phosphate buffer solution (PBS), respectively, which outperformances monometallic counterparts and comparable to the best bimetallic catalysts ever reported. The catalyst is highly stable because of the strong bonding between the bimetallic nanoparticle and rGO. Mechanism studies show that Ru 1 Pt 2 @rGO has a faster Volmer–Tafel mechanism in alkali, high-efficient H + transfer and increased H adsorption ability in acid, resulting in superior reaction kinetics. This work provides a new route for mass production of high-performance catalysts for practical applications at all pH values.

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Sustainable Materials and Technologies · 2024 · IF 8.6

Highly efficient nanosized MoS2/MoP heterocatalyst for enhancing hydrogen evolution reaction over a wide pH range

Mingyuan Zhu,Lijun Yu,Simiao Sha,Riyue Ge,Chi Cheng,Liming Dai,Sean Li,Bin Liu,Zhixue Qu,Wenxian Li

Energy consumption associated with the catalysts contributes partly to the high ohmic resistance arising from the low conductivity of the catalyst and poor charge transfer between nanoparticles, which has been difficult to study due to the complicated nanostructured framework of the catalysts. We constructed a novel heterostructure electrocatalyst (MoS 2 /MoP@NC) composed of nanosized MoS 2 /MoP heterostructures anchoring on hierarchical N-doped carbon for smoothing electron transfer in boosting hydrogen evolution reaction (HER). With the merits of large surface area, rapid charge transfer, and optimized electronic structure induced by charge transfer across the sufficient interface, the optimal MoS 2 /MoP@NC (MoSP) catalyst shows a competitive overpotential of 140 (0.5 M H 2 SO 4 ), 76 (1.0 M KOH), and 103 mV (0.5 M NaCl &1.0 M KOH) at 10 mA cm −2 , respectively. Raman experiment and Density functional theory (DFT) calculations reveal the formation of Mo-S-Mo bonds between MoS 2 and MoP, which favor enhancing the Femi level to facilitate the electron transfer, therefore regulating the electronic structure for the optimization of adsorption energy of hydrogen intermediate. Based on the experimental results, we constructed an energy consumption model of catalysts, where energy consumption comes from three aspects. The heterostructure design decreases the energy consumption of the catalysts greatly compared to the single-phase Mo-based catalyst of MoS 2 (78.0%) and MoP (45.2%) in alkaline electrolytes.

CAS / MDL: 62-31-7
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