JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yanjuan Huang,Xiuling Dai,Yujun Gong,Lingling Ren,Yong Luo,Yue Sun,Meixu Chen,Jingwen Jiang,Zilin Guan,Chunshun Zhao
Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6 + macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6 + macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect–cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.
研究领域:
生物医学工程
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药学
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组织工程
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外科研究
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
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IF 8.2
Ru Li,Yimei Ma,Anqi He,Yamin Pu,Xuanting Wan,Hongbao Sun,Ningyu Wang,Min Luo,Guan Wang,Yong Xia
The multi-kinase inhibitor sorafenib has shown potential to inhibit tumor cell growth and intra-tumoral angiogenesis by targeting several kinases, including VEGFR2 and RAF. Abnormal activation of the Ras/Raf/MAPK/ERK kinase cascade and the VEGF pathway is a common feature in breast cancer. However, the efficacy of sorafenib in breast cancer treatment remains limited. Recently, fasting has emerged as a promising non-pharmacological approach to modulate cancer metabolism and enhance the effectiveness of cancer therapies. In this study, we found that fasting significantly enhances the anti-cancer effects of sorafenib monotherapy and its combination with immunotherapy in breast cancer models without causing obvious side effects. This combined treatment effectively inhibits tumor cell proliferation and intra-tumoral angiogenesis. The fasting-induced reduction in peripheral blood glucose levels strongly correlated with enhanced sensitivity to sorafenib. Mechanistically, the combined treatment induced mitophagy, characterized by mitochondrial dysfunction and activation of the PINK1-Parkin pathway. Consequently, increased mitochondrial ROS levels promoted p53 expression, amplifying cell cycle arrest and apoptosis in breast cancer cells. Furthermore, fasting reduced lactate levels within the tumor, and the consequent glucose limitation synergized with sorafenib to activate AMPK, which in turn elevated PD-L1 expression in tumor cells, potentially enhancing their sensitivity to immunotherapy. In summary, our findings demonstrate that fasting and sorafenib, as a rational combination therapy, induce mitophagy, thereby enhancing sorafenib's efficacy in treating breast cancer through the ROS-driven p53 pathway. This study underscores the potential of fasting in breast cancer therapy and provides a foundation for optimizing the clinical application of sorafenib.
研究领域:
肿瘤学
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分子生物学
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代谢研究
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Qianqian Zhao,Min Gu,Mengnan Ni,Jinyu Li,Ting Wu,Senlin Zhu,Yupeng Zhou,Yawen Lu,Xiaolin Li,Huae Xu,Meiping Lu
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.
研究领域:
药学
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药物递送
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过敏与免疫学
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生物医学工程
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
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2025
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IF 3.3
Zhixin Zhang,Linli Zhao,Jiahui Wang,Hao Chen,Yan Lin,Fangbin Wang,Lu Wang,Juan Chen,Jian Liu,Xian Zhang
In beige adipocytes, UCP1-dependent thermogenesis can be driven by intracellular reactive oxygen species (ROS) generation. While ROS elevation also induces mast cell activation, serotonin synthesis and release from mast cells inhibits beige progenitor cell proliferation and browning. As a natural antioxidant and mast cell stabilizer, luteolin promotes adipocyte thermogenesis and inhibits mast cell activation. Thus, to activate adipocyte thermogenesis, how luteolin regulates ROS level in beige adipocytes and mast cells needs to be further investigated. In this study, mouse subcutaneous stromal vascular fraction (SVF) cells are induced to differentiate into beige adipocytes, and mouse bone marrow-derived mast cells (BMMCs) are activated with hydrogen peroxide (H 2 O 2 ). Intracellular ROS level is augmented in differentiated beige adipocytes and H 2 O 2 -activated BMMCs, and H 2 O 2 -activated BMMCs inhibited brown differentiation of SVF cells and thermogenesis of beige adipocytes. In beige adipocytes, unlike synthetic antioxidant N -acetylcysteine (NAC), luteolin elevates the expression of thermogenic and beige-selective marker genes and intracellular ROS generation. Contrarily, luteolin inhibits H 2 O 2 -induced mast cell activation and ROS generation. Further, luteolin partially reverses the inhibitory effects of H 2 O 2 -activated BMMCs on the brown differentiation of SVF cells and the thermogenesis of beige adipocytes. Molecular mechanistic studies demonstrate that luteolin regulates intracellular ROS level in beige adipocytes and mast cells via the nuclear factor erythroid 2-related factor 2 (Nrf2)/Catalase pathway. Altogether, as a ROS regulator, luteolin contrarily affects intracellular ROS generation in beige adipocytes and mast cells, and hence elevates adipocyte browning.
研究领域:
分子生物学
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代谢研究
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药理学
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DOI
PubMed
高影响因子
DRUG DELIVERY
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2023
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IF 6
Yaqin Tu,Wei Zhang,Guorun Fan,Chenming Zou,Jie Zhang,Nan Wu,Jiahui Ding,Wen Qing Zou,Hongjun Xiao,Songwei Tan
High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.
研究领域:
癌症治疗
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药学科学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
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2018
·Vol. 9
·期 7
·904-911
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IF 4.927
Bingkun Yan,Yan Zhang,Chao Wei,Yue Xu
Oxidation-responsive thioether-functional polymers have emerged as potential materials for biomedical applications. Herein, we report the straightforward synthesis of a well-defined biodegradable thioether-containing polycarbonate (mPEG-b-PS) based on the macrocyclic sulfur-substituted carbonate monomer (MS) using an enzyme-catalyzed ring-opening polymerization with the thioether groups situated on the backbone. NMR, FTIR and GPC techniques were employed to confirm the structure of the copolymers. Moreover, the thioether groups endowed the copolymers with rich ROS responsiveness and the oxidation mechanism was clarified according to in situ1H-NMR, FTIR and TGA data. In addition, the water contact angles testified that the hydrophilicity of the copolymers was greatly improved during the H2O2 triggered oxidation process. The thioether oxidation to polar sulfone and sulfoxide groups enabled us to tailor the copolymer's solubility profile; thus, the size, morphology and transmittance of the nanostructure changed according to the results obtained using DLS, TEM and UV techniques. Furthermore, CCK-8 assays showed that the thioether-containing polycarbonate and their oxidized products were non-toxic up to a tested concentration of 250 μg mL−1. Moreover, the mPEG-b-PS had a definite H2O2-triggered drug release behaviour. Therefore, these results highlight a facile synthesis of biodegradable thioether-containing polymers and provide a novel ROS responsive material platform for further cancer therapy and inflammation targeting.
研究领域:
材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Bioactive Materials
·
2023
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IF 18.9
Zhiguo Lu,Ruichen Zhao,Yi Li,Jianze Wang,Jing Guo,Chaobo Bai,Jing Chen,Jun Yang,Yiwan Geng,Tianlu Zhang,Yanyue Wu,Xiyue Jiao,Yining Wang,Junliang Yuan,Xin Zhang
Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
研究领域:
药理学
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纳米技术
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神经科学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Miaomiao Yao,Qi He,Yameng Tao,Xiaoyang Kang,Xinru Wu,Fangkai Shi,Yujia Wei,Jingjing Liu,Zhiyun Meng,Ruolan Gu,Hui Gan,Guifang Dou,Shuchen Liu,Yunbo Sun
Blue fluorescent carbon quantum dots (CDs) were synthesized by a one-step hydrothermal method using chitosan as the only raw material. This material overcomes multifunctional integration limitations in traditional dressings, achieving coordinated wound repair across all phases. During inflammation (0–3 days), CDs scavenge reactive oxygen species and suppress inflammatory factors (TNF-α↓49.63%, IL-6↓70.8%). In proliferation (3–7 days), they promote angiogenesis (CD31↑56.89%) and cell proliferation (Ki67↑74.3%). During remodeling (7–14 days), functional parallel collagen deposition occurs (collagen deposition 1.26× Celox group). The seamless “anti-inflammation/prohealing/remodeling” mechanism yielded 59% wound closure by day 3 postirradiation (vs Celox 37.34%). CDs synergistically activate Nrf2 while inhibiting NF-κB pathways, enabling combined anti-inflammatory/antioxidant regulation in irradiated environments. Nanoscale reconstruction retains chitosan’s hemostasis and avoids gene modification/vector loading via one-step synthesis (cost-reduced), with biosafety confirmed by acute toxicity tests. This study provides a prohealing nanomaterial and establishes a paradigm for traditional biomaterial redevelopment.
研究领域:
生物材料
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纳米医学
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炎症调控
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组织工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2023
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IF 10
Wenjing Mo,Shujie Liu,Xiaozhi Zhao,Fayun Wei,Yuhang Li,Xinan Sheng,Wenmin Cao,Meng Ding,Wenlong Zhang,Xiaoqing Chen,Longxiyu Meng,Sheng Yao,Wenli Diao,Hui Wei,Hongqian Guo
Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC-induced immunosuppression but also triggers differentiation and polarization of M2-TAMs. Herein, an ROS scavenging nanozyme, Zr-CeO, with enhanced superoxide dismutase- and catalase-like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr-CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2-TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer-associated fibroblasts. Furthermore, Zr-CeO enhances the antitumor effect of PD-1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr-CeO alone or combination therapy enhances T lymphocyte infiltration and IFN- γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided.
研究领域:
癌症免疫治疗
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纳米医学
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免疫学
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肿瘤微环境
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
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IF 5.8
Fujiang Li,Junfeng Ding,Zhenyu Li,Yan Rong,Chaoliang He,Xuesi Chen
In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and the antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogels demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogels effectively inhibited tumor growth, prolonged animal survival time and promoted antitumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogels exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective antitumor treatment and prevention of tumor reoccurrence.
研究领域:
生物材料学
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肿瘤免疫学
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药剂学
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产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2022
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IF 4.345
Songjiang Wu,Yanying Yang,Feiping Li,Lifu Huang,Zihua Han,Guanfu Wang,Hongyuan Yu,Haiping Li
Introduction Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time.Methods In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis.Results Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE.Conclusion Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2018
·Vol. 9
·期 1
·1-11
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IF 4.963
Li Qiang,Yin Yating,Zheng Yuqing,Chen Feifei,Jin Peisheng
Background Increased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. Autophagy is a molecular process that allows cells to degrade and recover damaged macromolecules, and closely interacts with apoptosis. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose.Methods Human ADSCs were cultured in normal or high-glucose medium for 6 h, 12 h, or 24 h. The effects of high glucose on ADSC autophagy, reactive oxygen species (ROS) production, and apoptosis were evaluated. The impact of autophagy on ROS production and apoptosis was explored by treatment with rapamycin or 3-methyladenine (3-MA). The c-jun kinase (JNK) signaling pathway was investigated by pharmacological disruption of SP600125.Results ADSCs subjected to high glucose stress showed an obvious induction of autophagy and apoptosis and a significant increase in intracellular ROS levels. The JNK signaling pathway was confirmed to be involved in high glucose-induced autophagy. Pre-treatment with SP600125 or N-acetylcysteine reversed the effects of high glucose on the JNK signaling pathway and autophagy-related proteins. Pretreatment of ADSCs with 3-MA under high glucose stress induced a further increase in ROS levels compared to those of high glucose-treated cells. Furthermore, ADSCs pretreated with 3-MA under high glucose stress showed a marked increase in apoptosis compared with that of the cells treated with high glucose. Conversely, pre-treatment with rapamycin inhibited the apoptosis of ADSCs.Conclusion sTaken together, our data suggest that autophagy may play a protective role in high glucose-induced apoptosis in ADSCs. ROS/JNK signaling is essential in upregulating high glucose-induced autophagy. This study provides new insights into the molecular mechanism of autophagy involved in high glucose-induced apoptosis in ADSCs.
研究领域:
细胞生物学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）