RESPIRATORY RESEARCH
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2025
·Vol. 26
·期 1
·1-17
·
IF 5
Ren Shencheng,Zhu Junkan,Shan Guangyao,Liang Jiaqi,Bian Yunyi,Lin Han,Shi Haochun,Pan Binyang,Zhao Guangyin,Yang Huiqin,Huang Xiaolong,Zhan Cheng,Ge Di,Bi Guoshu
Background Lung cancer remains the leading cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Despite extensive research efforts, the role of transcription factors in LUAD progression remains largely uncharacterized. In this study, we focused on ZNF266, a transcription factor whose impacts on LUAD have not been investigated. Methods Using high-throughput sequencing data, we observed a significant downregulation of ZNF266 expression in LUAD tissues. To validate this finding, we conducted a retrospective analysis of nearly three thousand LUAD patients’ data from public databases and our institution. Functional studies were performed using cell lines, organoids, and xenograft models to assess the role of ZNF266 in LUAD progression. RNA sequencing, chromatin immunoprecipitation, DNA pull-down assays, and dual-luciferase reporter assays were employed to elucidate the underlying mechanism. Additionally, adeno-associated virus (AAV)-mediated overexpression of ZNF266 was used to evaluate its therapeutic potential. Results Patients with low ZNF266 expression had poorer prognosis compared to those with high expression. ZNF266 inhibits the malignant phenotypes of LUAD, including proliferation, migration, and invasion. Mechanistically, ZNF266 binds to the promoter region of CA9, suppressing its transcription. This leads to a reduction in intracellular pH and subsequent inhibition of the mTOR signaling pathway, which is crucial for cancer cell growth and survival. Furthermore, AAV-mediated overexpression of ZNF266 significantly inhibited tumor growth in patient-derived xenograft models. Conclusions Our study demonstrated that ZNF266 inhibits LUAD progression in a pH-dependent manner via modulating CA9 expression, uncovering its therapeutic significance for LUAD treatment.
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JOURNAL OF MATERIALS CHEMISTRY
·
2012
·Vol. 22
·期 30
·15206-15214
·
IF 5.968
Wan-Fu Ma,Ke-Yi Wu,Jing Tang,Dian Li,Chuan Wei,Jia Guo,Shi-Long Wang,Chang-Chun Wang
A smart magnetic targeting drug carrier (MCNC/PAA) comprising an approximately 100 nm sized magnetic colloid nanocrystal cluster (MCNC) core and a pH-responsive cross-linked poly(acrylic acid) (PAA) shell is reported. The abundant carboxyl groups in the shell enable the resultant MCNC/PAA to easily load a large amount of doxorubicin (DOX) (up to 44.6%) via the strong interaction between the DOX and the carboxyl group in a neutral solution. Interestingly, a synergistic pH-responsive effect derived from the entrapped DOX and PAA network was found to effectively manipulate the drug releasing behavior at 37 °C. It was found that the premature release was highly restricted at a pH of 7.4, and upon reduction in pH from 7.4 to 5.0 or 4.0, a large amount of drug was rapidly released. Compared with the synthesized MCNC/PNIPAM, MCNC/PHEMA and MCNC/PDMAPMA nanocarriers, the MCNC/PAA was preferably suited to drug delivery. In addition, the composite nanocarriers could be tracked by magnetic resonance imaging (MRI). The cytotoxicity assay of MCNC/PAA to normal cells indicated that the composite nanospheres were biocompatible and suitable as drug carriers. Meanwhile, the DOX-loaded composite nanospheres had more potent cytotoxicity than free DOX to HeLa cells. These results clearly imply that the MCNC/PAA nanocarrier is a promising platform that can be applied to construct a smart drug delivery system with magnetic targeting and pH-stimulation, as well as tracking by MRI.
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RSC Advances
·
2024
·Vol. 14
·期 52
·38353-38363
·
IF 3.9
Yuan Ma,Yunfeng Tang,Jianwei Fan,Tianyu Sun,Xiaoyong Qiu,Luxing Wei,Xiaolai Zhang
Traditional hydrogels based on Schiff base reactions frequently encounter issues with rapid drug release when employed as drug delivery systems owing to their susceptibility to hydrolysis under acidic conditions. It is, therefore, necessary to implement improvements to regulate the drug release behavior. In this study, a dual-network and pH-responsive biopolysaccharide hydrogel was developed, which is self-healing, injectable and biocompatible. Most importantly, the hydrogel has excellent tunability for controlled drug release. The hydrogel consisted of a primary network of dibenzaldehyde-functionalized poly(ethylene glycol) (DP) and chitosan (CS) formed through a Schiff base reaction and a secondary network of sodium alginate (SA) and CS formed through electrostatic interactions. It was found that the DP–CS–2%SA hydrogel can prolong the release duration up to four-fold compared to the single-network DP–CS hydrogel at a given release threshold. Significantly, by adjusting the relationship between the two effects through the amount of SA, the release modifiability of drug delivery systems has been greatly enhanced. This study could significantly enhance the tunability of hydrogel drug delivery systems.
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Applied Materials Today
·
2024
·
IF 7.2
Yanping Feng,Zizhuo Liu,Yongxing Feng,Jingjing Wang,Jinfa Chen,Zhihong Dong,Youzhuan Xie,Congqin Ning
Bacterial infections can slow down wound healing and pose a threat to human health, which remains a challenging issue in clinical practice. The rise of nanozymes has provided new therapeutic approaches for antimicrobial treatment. Here, we report pH-responsive copper selenide nanoparticles (Cu 1.79 Se, hereafter referred to as CuSe), which exhibits peroxidase (POD)-like activity under weakly acid bacterial infection conditions, generating highly reactive hydroxyl radicals (·OH) that kill bacteria and alleviate wound infections. In the later stages of wound healing, it is neutral or weakly alkaline, the CuSe nanoparticles shows catalase (CAT) and superoxide dismutase (SOD)-like activities, clearing excessive reactive oxygen species (ROS) and producing O 2 , thus protecting normal tissues from damage caused by both external and endogenous ROS. The above feature helps damaged tissue cells regain their ability to proliferate and migrate, also promotes angiogenesis, achieving a "two birds with one stone" effect. It is expected that the CuSe nanoparticles could be a promising antimicrobial agent for wound healing.
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BIOMATERIALS
·
2011
·
IF 7.883
Yunlu Dai,Cuimiao Zhang,Ziyong Cheng,Ping’an Ma,Chunxia Li,Xiaojiao Kang,Dongmei Yang,Jun Lin
In this study, we design a controlled release system based on CaF 2 :Ce 3+ /Tb 3+ -poly(acrylic acid) (PAA) composite microspheres , which were fabricated by filling the pH-responsive PAA inside CaF 2 :Ce 3+ /Tb 3+ hollow spheres via photopolymerization route. The CaF 2 :Ce 3+ /Tb 3+ hollow spheres prepared by hydrothermal route possess mesoporous structure and show strong green fluorescence from Tb 3+ under UV excitation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, was used as a model drug to evaluate the loading and controlled release behaviors of the composite microspheres due to the good biocompatibility of the samples using MTT assay . The composite carriers provide a strongly pH-dependent drug release behavior owing to the intrinsic property of PAA and its interactions with DOX. The endocytosis process of drug-loaded microspheres was observed using confocal laser scanning microscopy (CLSM) and the in vitro cytotoxic effect against SKOV3 ovarian cancer cells of the DOX-loaded carriers was investigated. In addition, the extent of drug release could be monitored by the altering of photoluminescence (PL) intensity of CaF 2 :Ce 3+ /Tb 3+ . Considering the good biocompatibility, high drug loading content and pH-dependent drug release of the materials, these hybrid luminescent microspheres have potential applications in drug controlled release and disease therapy.
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Gels
·
2024
·Vol. 10
·期 12
·840
·
IF 5
Xinxia Zhang,Yafeng Ding,Jiangtao Zhou,Qianqian Xu,Ting Li,Li Wang
The study aimed to prepare complex gels of sonicated quinoa protein (QP) and polysaccharides, comparing the effects of different protein components and pH on gel properties. FTIR analysis demonstrated that the β-structure in protein at pH 7.0 was enhanced by ultrasonic treatment, which could promote the formation of a gel network. Moreover, XG-AG (gel prepared by xanthan gum and albumin) and XG-GG (gel prepared by xanthan gum and globulin) exhibited higher levels of disulfide bonds and free sulfhydryl groups in the gel, requiring more energy to break the intermolecular sulfide bonds during heating. Under the same heating conditions, the rheological properties and gel strength of XG-UQPG (gel prepared by xanthan gum and ultrasonically treated QP) were superior to those of XG-UGG (gel prepared by xanthan gum and ultrasonically treated globulin) and XG-UAG (gel prepared by xanthan gum and ultrasonically treated albumin). Additionally, XG-UGG (pH 7.0) demonstrated the highest water holding capacity (WHC) and oil holding capacity (OHC). This was attributed to the disulfide bonds created in the proteins by the ultrasound treatment, encouraging them to interact to form more uniform holes in gel that can hold more water/oil molecules. Conversely, at pH 4.5, the WHCs of the gels were reduced due to the presence of rougher protein structures. These findings shed light on the impact of protein composition on gel properties and offer insights into enhancing the quality of quinoa protein gel.
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ACS ES&T Water
·
2025
·
IF 4.3
Wen-Long Wang,Peng-Hui Liu,Jung-Hyun Son,Hang Su,Min-Yong Lee,Hong-Ying Hu,Qian-Yuan Wu,Uwe Hübner
The combination of ozonation and Mn(II) (O3/Mn(II)) is expected to synergistically eliminate recalcitrant organic micropollutants in water. However, the decay of O3, formation of •OH and reactive manganese species (RMnSs), and synergism in micropollutant degradation have not been comprehensively understood. Herein, the synergism of O3 and Mn(II) was observed to be pH-dependent. Compared to ozonation alone, O3/Mn(II) preferentially formed Mn(V and VI) and slightly increased •OH yield (from 0.22 to 0.30) at acidic pH 4–5, while it preferentially formed Mn(VII) and significantly increased OH yield (from 0.52 to 0.74) at circumneutral pH 6–7. Thereafter, O3/Mn(II) prominently increased RMnS exposure at acidic pH, while it dramatically diminished O3-exposurse to increase •OH exposure at circumneutral pH. As a result, O3/Mn(II) outperformed ozonation alone for the degradation of various O3-resistant micropollutants (3.7–7.9 times faster). For example, the RMnSs (82.7% contribution) and •OH (84.2% contribution) were the dominant contributors to the degradation of the isothiazolinone biocide (5-chloro-2-methyl-4-isothiazolin-3-one) at acidic and circumneutral pH, respectively. Mn(II) can enhance the removal of O3-resistant micropollutants in relatively clean waters (e.g., tap water), but its effectiveness was limited in more contaminated waters (e.g., WWTP effluent). These findings support the practice and pH optimization of the O3/Mn(II) in various water types.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Miaoyu Gan,Ailing Cao,Luyun Cai,Xia Xiang,Jian Li,Qian Luan
Oral administration of astaxanthin (AST), a potent antioxidant, is limited owing to its low solubility, physicochemical stability, and bioavailability. This study developed pH-responsive nanocarriers by the electrostatic self-assembly of 2,2,6,6-tetramethylpiperidine-1-oxyradical (TEMPO)-oxidized cellulose nanofibers (TCNFs) and chitosan (CS) to enhance the intestinal delivery of AST. The TCNF/CS@AST nanoparticles were optimized through single-factor experiments and Box–Behnken design, subsequently overcoming the hydrophobicity of AST and demonstrating improved stability against environmental stressors and controlled release in the intestinal environment. Transmission electron microscopy confirmed the near-spherical shape of these nanoparticles, with an average hydrodynamic diameter of 64 nm. TCNF/CS@AST enhanced the antioxidant effectiveness of AST after digestion and in lipopolysaccharide-stimulated RAW 264.7 cells while demonstrating good cellular compatibility. These nanoparticles present a promising strategy for the oral delivery of hydrophobic bioactive compounds orally, with potential applications in precision nutrition.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Congling Yang,Qianying Guo,Xinchun Wang,Hongmei Chen,Huan Tan,Bo Feng,Jie Weng
Multi-responsive drug-delivery systems have been widely explored to enable specific delivery to target sites. Here, interleukin-4 (IL-4), an anti-inflammatory cytokine, is first encapsulated in situ inside a zeolitic imidazolate framework (ZIF-8) to form IL-4@ZIF-8, which is subsequently coated with a diselenide block copolymer to obtain IL-4@ZIF-8@Se-Se-polymer. This delivery system enables redox-responsive release of IL-4 by the diselenide copolymer and a pH-triggered release by ZIF-8. Moreover, IL-4 release is precisely controlled stepwise by the stimuli response, with the dissociation of the diselenide copolymer, and breakdown of the ZIF-8 structure. The targeted release property of the IL-4@ZIF-8@Se-Se-polymer endows the materials with efficient macrophage immune regulation, as systematically demonstrated in vitro. This study provides an effective example of the delivery and on-demand release of IL-4, and may find promising applications in tissue engineering for the management of inflammation.
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ACS Applied Nano Materials
·
2024
·
IF 5.3
Nuo Li,Ludan Zhang,Kaijun Sun,Junheng Liu,Zixuan Wang,Yujing Wang,Huinan Lu,Wenjun Xiang,Hailin Yang,Rupei Tang,Guoqing Yan
5-Fluorouracil (5FU) and its derivatives have been widely used for cancer treatment; however they fail to achieve selective chemotherapy. Herein, this work highlights a successful development of a pH-sensitive aliphatic 5-fluorouracil (5FU) derivative prodrug, which is synthesized via chemically linking 5FU and stearyl alcohol (SA) using ortho ester linkage. It can further self-assemble into a synergistic small molecule nanodrug through a noncovalent interaction with doxorubicin (DOX). The nanodrug displays precise structure and high drug loading (more than 15% of drug loading content (DLC) and 87% of drug loading efficiency (DLE)). SA and ortho ester linkages endow the nanodrug with high lipophilicity on tumor cell membrane and tumoral intracellular pH response, respectively. The nanodrug also exhibits a slightly negatively charged surface (−0.513 mV) at physiological pH (7.4) and a large-to-small size change from 176.2 to 128.9 nm at tumoral intracellular pH (5.0). These superior characteristics endow the nanodrugs with blood circulation stability, selective tumor accumulation, improved cellular uptake, efficient drug release, as well as synergistic effect on tumor cells, thereby significantly inhibiting tumor growth (smaller than initial tumor size), reducing side effects, and prolonging survival time. Thus, such a pH-sensitive small molecule nanodrug self-assembled from the aliphatic 5FU derivative and DOX has a great potential for selective synergistic cancer therapy, greatly advancing their clinical use.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Qingxi Hu,Wenxiang Tang,Yongteng Song,Haiguang Zhang
Cardiovascular diseases pose a serious threat to human life and health. Vascular stent intervention surgery is currently the main method for treating cardiovascular diseases in the clinic, but the implantation of bare mental vascular stents can easily cause surgical infection. Fortunately, covering the surface of vascular stents with antibacterial membranes can effectively solve this problem. Therefore, in this work, an electrospun nanofibers membrane loaded with amoxicillin (AMX) was developed via coaxial electrospinning, and the release of AMX can be controlled by a pH-responsive process. The nanofibers (PEO-AMX/PCL-SF) had core-shell structures, with polyethylene oxide (PEO) containing AMX as the core layer and silk fibroin (SF) and polycaprolactone (PCL) as the shell layer. The weakly acidic environment caused by bacterial metabolism could cause the pH-responsive of SF in the nanofiber shell layer, resulting in the release of AMX in the core layer for antibacterial purposes. The PEO-AMX/PCL-SF nanofibers membrane exhibited excellent physicochemical properties, with a tensile strength of 3.25 ± 0.04 MPa and a water contact angle of 41.99 ± 1.43°. Furthermore, the membrane showed excellent pH-responsive drug release characteristics and antibacterial properties. In vivo and in vitro experiments suggested that the prepared nanofibers membrane has great biocompatibility and antibacterial properties, which has the potential to prevent and treat surgical infection after vascular stent implantation.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Jinke Guo,Shouzhi Yan,Md All Amin Newton,Binjie Xin,Zhuoming Chen
Managing wound exudate, alleviating wound inflammation, and monitoring the healing process are the current focus of wound dressing research. However, the preparation of multifunctional dressings that simultaneously perform these functions remains a challenge. In this study, a pH-responsive Janus composite membrane with unidirectional moisture drainage and antioxidant properties is proposed for the wound healing process. This Janus composite membrane takes advantage of the difference in wettability between the hydrophilic polyacrylonitrile (PAN) layer and the hydrophobic polylactic acid (PLA) layer, which allows the fluid to be exported within 3 s and reduces the adhesion to the wound site. When the fibrous membrane was wetted, curcumin encapsulated in the fibers could be effectively released with a high antioxidant activity of 86.82 %. In response to pH changes during the wound healing process, the Janus composite membrane displays different colors under different conditions, which can be used to monitor wound healing. In addition, the biocompatibility of this Janus composite membrane increases the potential for its clinical use as a multifunctional wound dressing.
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