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Journal of Biomedical Nanotechnology · 2016 ·Vol. 12 ·期 8 ·1688-1698 · IF 3.929

A pH-Sensitive Nanosystem Based on Carboxymethyl Chitosan for Tumor-Targeted Delivery of Daunorubicin

Zhang Xueqiong,Zhang Hong,Yin Liangquan,Hu Rui,Qiu Tong,Yin Yihua,Xiong Xiong,Zheng Hua,Wang Qun

Nanoparticles, such as polymeric micelles, are currently regarded as effective drug delivery vehicles. In this study, a series of carboxymethyl chitosan/daunorubicin (CMCS/DNR) conjugates with macromolecular carriers of different molecular weights (MWs) were prepared and structurally characterized by Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR spectroscopy. The results indicated that the MWs of the carriers greatly influenced the drug loading capacity. DNR was conjugated to the polymer via an acid-sensitive hydrazone linkage susceptible to hydrolysis at pH 5–6, thereby enabling intracellular DNR release. In aqueous media, the conjugates spontaneously formed nano-sized particles with core–shell structures (CMCS and DNR as the shell and core, respectively). Dynamic light scattering (DLS) and trans-mission electron microscopy (TEM) indicated that the prepared nanoparticles were spherical in shape with diameters of 100–200 nm and had a slight negative surface charge. In addition, in vitro drug release studies demonstrated that the micelles were highly sensitive to mild acidic conditions (pH 5.0) but remained reasonably stable at pH 6.5 and pH 7.4. Importantly, cell counting kit-8 (CCK-8) assays demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa cells, with the IC50 being approximately 2 times higher than that of free-DNR. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the CMCS-hyd-DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer cells. Taken together, the developed CMCS based pH-sensitive nanosystem may be a potential drug delivery vehicle for cancer therapy.

✓ 已验证 DOI PubMed 高影响因子
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BIOMATERIALS · 2014 · IF 8.312

Hybrid polymeric micelles based on bioactive polypeptides as pH-responsive delivery systems against melanoma

Qi-Ming Wang,Zhonggao Gao,Shan Liu,Bo Fan,Lin Kang,Wei Huang,Mingji Jin

The bioactive polymer poly( l -glutamic acid) n - b -poly( d , l -lactic acid) m was synthesized and used to form doxorubicin-loaded hybrid polymeric micelles to treat melanoma. These polymers exhibited pH-responsive changes in conformation, which controlled the diverse functionalities of the micelles. During circulation, poly( l -glutamic acid) n - b -poly( d , l -lactic acid) m protected Tat peptides on the micelles from proteolysis . Under tumor-acidic conditions, polymers with shorter poly( l -glutamic acid) blocks underwent a conformational change to form channels that accelerated the release of doxorubicin . The conformational change also exposed the Tat peptides to tumor cells, thereby promoting cellular internalization of the micelles. Enhanced cellular uptake of the micelles induced significant apoptosis of A375 melanoma cells in tumor-acidic conditions. In vivo studies demonstrated that the micelles with shorter poly( l -glutamic acid) blocks could effectively accumulate in tumor tissues, suppress tumor growth and help maintain the body weight of tumor-bearing mice. However, micelles with longer poly( l -glutamic acid) blocks did not undergo a conformational change under acidic conditions and performed poorly in both in vitro and in vivo evaluations. Our work provides a strategy for applying bioactive polymers to the rational construction of pH-responsive delivery systems for solid tumors and lends insight into possible conformational effects on the bioactivity of drug carriers.

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BIOMACROMOLECULES · 2020 · IF 6.092

Ratiometric Fluorescent Mapping of pH and Glutathione Dictates Intracellular Transport Pathways of Micellar Nanoparticles

Zexuan Ding,Guhuan Liu,Jinming Hu

Visualization of intracellular transport pathways is crucial to investigate the internalization mechanism and understand the intracellular behavior of nanomaterials. Herein, we rationalized the design of micellar nanoparticles (NPs) for ratiometric fluorescent mapping of intracellular pH and glutathione (GSH), two essential parameters for maintaining normal cellular functions. Specifically, pH-sensitive naphthalimide-based probe (NPI) and pH-inert rhodamine B (RhB) were covalently labeled to double hydrophilic block copolymers (DHBCs) using the thiolactone chemistry, enabling the covalent attachment of NPI and RhB to one molecule with a redox-responsive disulfide linkage. The dually labeled DHBCs exhibited blue/orange dual emissions in acidic pH, which was further converted into green/orange dual emissions in neutral pH because of the deprotonation of NPI moieties and the sole green emission in the presence of GSH at neutral pH because of the decreased Förster resonance energy transfer efficiency between an NPI donor and an RhB acceptor as a result of GSH-mediated cleavage of disulfide bonds. These remarkable ratiometric fluorescence changes allowed for not only the simultaneous mapping of the intracellular pH and GSH but also the intracellular transport pathways of internalized NPs.

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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2021 · IF 8.128

Multi-functional rhodamine-based chitosan hydrogels as colorimetric Hg2+ adsorbents and pH-triggered biosensors

Xiaoyong Qiu,Jun Huang,Hui Wang,Yulu Qi,Jiwei Cui,Jingcheng Hao

Hypothesis Water contamination from heavy metal ions is a major global environmental concern. Adsorbents based on biomaterials have been demonstrated to possess remarkable removal efficiency for metal ions, but the adsorption model of biosorbents is not clear and much efforts should be devoted to study the adsorption behaviors and understand the adsorption mechanism. Experiments The multifunctional rhodamine-modified chitosan (RMC) hydrogel for Hg 2+ adsorption with fluorescent turn-ON properties was fabricated through grafting the rhodamine-modified poly (ethylene glycol) benzaldehyde (RM-PEG) onto the hydrogel network serving as the fluorescence/colorimetric sensing receptor. The adsorption behaviors and colorimetric sensing mechanism of RMC hydrogel towards Hg 2+ were investigated in detail. Findings RMC hydrogel can remove more than 96.5% of Hg 2+ from aqueous solution with significant fluorescence response and colorimetric change. The high adsorption selectivity and colorimetric sensing mechanism of RMC hydrogel towards Hg 2+ can be explained by the hard and soft acid/base (HSAB) theory. The O atom in hydroxyl and carbonyl groups together with the N atom in amine/imine groups of RMC hydrogel play a vital role in the adsorption of Hg 2+ , while the colorimetric response and fluorescence enhancement of the hydrogel after adsorption are attributed to the specific spiro-lactam structure of rhodamine moieties. The adsorption isotherms and kinetics were investigated and well described by Freundlich isotherm and pseudo-second-order kinetic model . Furthermore, RM-PEG showed low cytotoxicity towards mouse embryonic fibroblast cells and RMC hydrogel can be used as a fluorescent pH indicator from 4.2 to 7.4, demonstrating the potential applications of RMC hydrogel in biological diagnosis.

✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2025 · IF 5.6

Fighting periodontitis with a pH-triggered nanocoating: A sustained-release strategy for simvastatin delivery

Siyu Du,Yi Zheng,Yabing Chen,Yijing Guo,Xinyue Kang,Lei Wang

The growing incidence of periodontitis demands innovative therapies, as current drug treatments are limited by short retention times, rapid clearance, and the risk of antimicrobial resistance. This study introduces a novel pH-responsive nano-miclle system for simvastatin (SIM) delivery. Its core innovation lies in being the first system ((SIM NP)n) of its kind to be stabilized by a cross-linked "outer shell," which significantly enhances its stability and controlled release capabilities. This "smart" system remains stable in a neutral environment (pH 7.4), preventing premature drug release. However, upon encountering the acidic inflammatory microenvironment of periodontitis, the shell degrades, triggering the sustained release of SIM directly at the site of inflammation. In vitro studies demonstrated that the SIM-loaded micelles possess potent immunomodulatory effects: they effectively suppressed pro-inflammatory M1 macrophage polarization (decreasing IL-1β, iNOS) while promoting anti-inflammatory M2 macrophage polarization (increasing Arg-1, IL-10). Mechanistic investigation confirmed this therapeutic effect is mediated by the PI3K/AKT/mTOR signaling pathway. More importantly, in a mouse model of periodontitis, the nano-micelles significantly reduced alveolar bone resorption, demonstrating potent anti-inflammatory and bone-protective efficacy in vivo. In conclusion, this "smart" pH-triggered delivery system for SIM offers a highly promising and effective strategy to overcome the limitations of traditional therapies, providing a new targeted path for the treatment of periodontitis.

CAS / MDL: 79902-63-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

pH-Tunable gliadin–chitosan–lipase ternary complexes enabling efficient interfacial synthesis of phytosterol ester

Huanyu Zheng,Ji Zhang,Zhouliang Sun,Mengqi Wang,Yufei Zhang,Mingming Zheng

Nature employs non-catalytic scaffold proteins to achieve precise enzyme positioning and enhanced catalysis. However, mimicking this approach with food-grade macromolecular materials remains a significant challenge. Herein, we introduce a pH-tunable gliadin-chitosan matrix designed to act as a bioinspired scaffold. It spontaneously self-assembles with lipase into stable ternary complex, gliadin-chitosan-lipase (GCL), through robust hydrogen bonding and hydrophobic interactions (∆G_binding = −331.7 kJ‧mol −1 ) immobilize lipase AYS in an optimally active conformation. Upon addition to an oil-water mixture at pH 7, GCL particles adsorb at the interface, creating a highly efficient Pickering interfacial biocatalysis (PIB) system. When applied to the synthesis of sterol esters via interesterification with flaxseed oil, the GCL-stabllized PIB system achieved an 81.4 % yield within 6 h, a relative conversion rate of almost three times that of free lipase (31.8 %), and maintained 73.4 % of its initial activity after five consecutive cycles. Its compatibility extended to six commercial oils. Molecular dynamics results indicated that lipase acts as a regulatory element, suppressing global fluctuations to generate stable structures with high catalytic activity, thereby preparing the interface for biocatalysis. This work establishes a sustainable, scalable platform for functional lipid production and provides a blueprint for next-generation biomacromolecular enzyme carriers.

CAS / MDL: 1492-30-4
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·10863 · IF 15.7

Lattice-hydrogen cycling mechanism enables pH-universal hydrogen evolution at ampere-level current densities

Zhang Yan,Feng Biao,Tian Jingyi,Zhou Shiqi,Zhou Changkai,Chen Yiqun,Xia Xiaoli,Wang Xizhang,Yang Lijun,Peng Luming,Wu Qiang,Huang Hongwen,Hu Zheng

Controllable supply of hydrogen intermediate across a wide pH range is crucial for electroreduction reactions, but is hindered by pH-dependent hydrogen species formation on conventional catalysts. We report a lattice-hydrogen cycling mechanism that dissociates hydrogen intermediate availability from electrolyte pH. By integrating proton-blocking Ru with thermally-hydrogenated H x WO 3 , we create a dynamic hydrogen reservoir, enabling efficient hydrogen supply. In-situ Raman spectroscopy, isotopic labeling, and theoretical simulations reveal the lattice hydrogen in H x WO 3 migrates swiftly to Ru active sites via low-energy-barrier pathways, while consumed hydrogen is spontaneously replenished via proton adsorption (acidic) or water dissociation (alkaline/neutral). Consequently, this catalyst achieves a competitive pH-universal performance for hydrogen evolution reaction, with low overpotentials (125 mV acidic, 142 mV alkaline, 219 mV neutral @1 A cm -2 ) alongside 500-hour stability.

CAS / MDL: 7778-77-0
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

MnO2-coated CaO2 nanoparticles as pH-responsive oxygen self-sufficient carriers to potentiate radioimmunotherapy

Wei Li,Chunjie Wang,Yujie Zhu,Yangguang Zhang,Hengze Ding,Linqi Zhu,Wei Zhou,Yongyou Wu,Liangzhu Feng

Radioimmunotherapy represents a clinically available combination strategy for treating a broad range of solid tumors, however, its therapeutic efficacy remains significantly compromised by tumor hypoxia due to the inhibition of cytotoxicity and the suppression of antitumor immunity activation. Herein, we synthesized a pH-responsive oxygen-releasing nanomedicine (denoted as an oxygen nanotank) by growing a thin manganese dioxide (MnO 2 ) layer onto calcium hyperoxide (CaO 2 ) nanoparticles through an in-situ oxidation process to enhance radioimmunotherapy. Using a two-step liposomal coating strategy, we obtained CaO 2 @MnO 2 -PEG, which exhibited excellent physiological stability, with MnO 2 functioned as a catalase-like nanozyme to enable pH-dependent oxygen generation. This nanomedicine significantly enhanced the X-ray irradiation induced cytotoxicity against hypoxic tumor cells by amplifying intracellular reactive oxygen species. After intravenous injection, CaO 2 @MnO 2 -PEG specifically accumulated in tumor tissues and substantially alleviated hypoxia, resulting in enhanced therapeutic outcomes of X-ray-mediated external radiotherapy in a subcutaneous CT26 tumor model. Furthermore, combining CaO 2 @MnO 2 -PEG with immune checkpoint blockade therapy achieved synergistic tumor suppression by concurrently activating innate and adaptive immune responses. This study establishes a controllable synthesis method for pH-responsive oxygen nanotanks, effectively addressing hypoxia-induced therapeutic resistance in radioimmunotherapy.

CAS / MDL: 13446-34-9
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Small · 2025 · IF 12.1

Reshape Intracellular/Extracellular pH for Enhanced Nanocatalytic Ferroptosis and cGAS-STING Activation Induced Immunotherapy

Jinglang Gong,Hongxiang Huang,Maoyu Gao,Yiling Ruan,Ruifang Chen,Yaoting Li,Shouju Wang,Xiaolian Sun

Nanometal-based therapies face challenges arising from the overexpression of proton efflux transporters in cancer cells, which acidifies the extracellular tumor microenvironment (TME) while preserving a relatively neutral intracellular pH, thereby compromising therapeutic efficacy and fostering an immunosuppressive TME. Here, we integrate the proton pump inhibitor pantoprazole (PTZ) with manganese ferrite nanoparticles (MFNs) within an acidity-responsive polymer for enhanced ferroptosis and cGAS-STING activation mediated immunotherapy. This assembly (PTZ/MFNAs) facilitates tumor accumulation through the enhanced permeability and retention effect while initially restricting the release of metal ions. Upon reaching the tumor site, PTZ release increases intracellular acidity, which further triggers assembly disintegration, accelerates the release of iron and manganese ions, and neutralizes the extracellular microenvironment to alleviate immunosuppression. The released manganese ions synergistically collaborate with iron ions to amplify reactive oxygen species (ROS) generation for ferroptosis while activating the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway, stimulating innate immunity. This potentiation of innate immunity, coupled with the reversal of TME immunosuppression, collectively and effectively inhibits tumor growth and metastasis. Therefore, the PTZ/MFNAs co-delivery system represents a promising pH-modulation strategy to enhance iron/manganese ions-mediated ferroptosis and cGAS-STING activation-induced immunotherapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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KEY ENGINEERING MATERIALS · 2014 · IF 0

The Effect of pH of the Aging Solution on Microstructure of Silica/Zirconia Aerogel

Jian He,Xiao Lei Li,Hui Ming Ji,Qing Pu Wang

ZrO2 wet gel was prepared using zirconium n-butoxide as precursor and 1,2-propylene oxide (PO) as a gelation agent in sol-gel process. Then, tetraethoxysilane (TEOS) was used to strengthen the wet gel in aging process. Finally, the monolithic silica/zirconia aerogel was obtained by supercritical fluid drying. N2 adsorption-desorption method, scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR) were used to characterize microstructure of the aerogel. The influence of pH of the aging solution on microstructure of silica/zirconia aerogel was studied. The results indicate that the particle size distribution of SiO2/ZrO2 aerogel was more uniform and less aggregate when aging in acid solution. However, the average pore diameter and particle size of SiO2/ZrO2 aerogel was increased by aging in alkaline solution. Aging in alkaline condition was useful for largening the pore size of SiO2/ZrO2 aerogel, and the maximum specific surface area and pore volume were obtained at pH=9. Meanwhile, different reactions were produced between the acid/alkaline solution and the hydroxyl of SiO2/ZrO2 aerogel, and the ester group/amino group was obtained relatively which can modify the network of aerogel and decrease the shrinkage of aerogel during the supercritical fluid drying.

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SPECTROSCOPY LETTERS · 2017 · IF 0.794

Multi-wavelength spectrophotometric determination of pH using phenol red–doped sol–gel film sensors

Hongliang Wang,Baohua Liu,Zhengguang Li,Lei Yang

Dye leakage and the nonlinear relationship between absorbance and pH affect the pH measurement precision of absorption-based optic sensors and limit their application. Based on the preparation of a transparent sol–gel thin film with a phenol red indicator, this work assumed that the absorbancies had an exponential relationship to the concentrations of the indicator, and the multi-wavelength equation for the pH was derived as follows: where n is the exponential coefficient, e1, e2, and e3 are the extinction coefficient ratios, and R is the ratio of the absorbancies. The calculation parameters for an immobilized phenol red film were pKa = 8.577, e1 = 0.0191, e2 = 1.530, e3 = 0.2992, and n = 0.6322, while those for an immobilized phenol red/Triton X-100 film were pKa = 8.612, e1 = 0.0507, e2 = 1.501, e3 = 0.3687, and n = 0.3931. The correspondence between the calculated pKa and the pKa from the calibration curve verifies the equation. The calculation parameters remain stable as the indicator content is increased, but change with an increase in the Triton X-100 content. Using the equation, the calculated pH shows stable behavior over a long duration regardless of dye leakage, and the calculated precision is 0.0053. The method provides drift-free and precise water pH measurements for R that is not dependent on the total concentration of the indicator, and can be applied to online monitoring.

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CARBOHYDRATE POLYMERS · 2015 · IF 4.074

Dual pH and temperature responsive hydrogels based on β-cyclodextrin derivatives for atorvastatin delivery

Kaiwen Yang,Sicheng Wan,Binbin Chen,Wenxia Gao,Jiuxi Chen,Miaochang Liu,Bin He,Huayue Wu

2-Methylacrylic acid modified β-cyclodextrin was copolymerized with 2-methylacrylic acid and N,N′-methylene diacrylamide to fabricate dual pH and temperature responsive hydrogels for the controlled release of atorvastatin. The swelling behaviors, pH and temperature responsive atorvastatin release profiles of the hydrogels were investigated. The results indicated that the hydrogel prepared in DMSO exhibited the best swelling rate, which was 51 for 10   min and 252 for 16   h when immersed in medium of buffer solution with pH   =   8.06. The media with low (pH   ≤   3.84) and high (pH   ≥   10.34) pH values would reduce the swelling rate of hydrogels. The swelling of the hydrogel was increased with increasing temperature from 30   °C to 45   °C. Atorvastatin was loaded in the hydrogel for drug release investigation. The cumulative release rate of atorvastatin was as high as 90.5% in pH   =   8.06 buffer solution. The solubility of atorvastatin was improved from 0.13 to 1.2   mg/mL in the hydrogel.

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