MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 12
·2100229
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IF 4.979
Fangqin Song,Siqi Li,Chuanhao Sun,Ying Ji,Yan Zhang
The integration of hypoxia-activated chemotherapy with photodynamic therapy (PDT) has newly become a potent strategy for tumor treatment. Herein, a reactive oxygen species (ROS)-responsive drug carriers (PS@AQ4N/mPEG- b -PSe NPs) are fabricated based on the amphiphilic selenium-containing methoxy poly(ethylene glycol)-polycarbonate (mPEG- b -PSe), the hydrophobic photosensitizer (PS), and hypoxia-activated prodrug Banoxantrone (AQ4N). The obtained nanoparticles are spherical with an average diameter of 100 nm as characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS) respectively. The encapsulation efficiency of the PS and AQ4N reaches 92.83% and 51.04% at different conditions, respectively, by UV–vis spectrophotometer. It is found that the drug release is accelerated due to the good ROS responsiveness of mPEG- b -PSe and the cumulative release of AQ4N is up to 89% within 30 h. The cell test demonstrates that the nanoparticles dissociate when triggered by the ROS stimuli in the cancer cells, thus the PS is exposed to more oxygen and the ROS generation efficiency is enhanced accordingly. The consumption of oxygen during PDT leads to the increased tumor hypoxia, and subsequently activates AQ4N into cytotoxic counterpart to inhibit tumor growth. Therefore, the synergistic therapeutic efficacy demonstrates this drug delivery has great potential for antitumor therapy.
研究领域:
药学
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纳米技术
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癌症治疗
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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
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ye Zhao,Yao Liu,Ran Liao,Pan Ran,Yuan Liu,Zixuan Li,Jichun Shao,Long Zhao
Sonodynamic therapy offers a highly accurate treatment for bacterial infections; however, its antibacterial efficacy is hindered by bacterial biofilms that limit the penetration of sonosensitizers. Herein, a nitric oxide (NO)-driven mushroom-like Janus nanomotor (BT@PDA-La) based on the unilateral coating of polydopamine (PDA) on piezoelectric tetragonal barium titanate (BT) and further modified with l-arginine (l-Arg) on the PDA side is fabricated. In the infected microenvironment with high levels of H2O2, NO is produced unilaterally from BT@PDA-La, thus leading to its self-propelled movement and facilitating its permeability in the biofilm. Under ultrasonic vibrations, the piezoelectric effect of BT@PDA-La is triggered by the exogenous mechanical wave, and toxic reactive oxygen species (ROS) are efficiently generated via an in situ catalytic reaction. The synergistic treatment with ROS/NO achieved the destruction of biofilms and embedded drug-resistant bacteria in vitro. Importantly, BT@PDA-La exhibits excellent biofilm penetration capacity, effectively eliminating biofilm infection while accelerating the healing of infected muscles by alleviating oxidative stress, regulating inflammatory factors, and accelerating angiogenesis. Collectively, this study provides a promising strategy for enhancing the penetration of pathological environment-driven nanomaterials through biofilms and advances the application of nanomotors for the therapy of bacterial infections in clinical medicine.
研究领域:
纳米技术
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生物医学工程
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微生物学
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治疗药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Tao Zhang,Yanjuan Huang,Yujun Gong,Xianmin Shi,Danni Xiao,Lingling Ren,Xiuling Dai,Zishan Zeng,Chunshun Zhao
Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde ( CHO). Further, the double crosslinked AHBC/PSC hydrogel was successfully fabricated between AHBC and PSC via forming dynamic covalent acylhydrazone bonds and borate ester bonds. Results showed that AHBC/PSC hydrogel had in situ gelation behavior, satisfactory mechanical properties (storage modulus of about 1 kPa and loss factor Tan δ of about 0.5), suitable wet tissue adhesion strength of about 2.3 kPa on rat abdominal wall, and good biocompatibility, achieving an ideal physical barrier. Particularly, CGA could be responsively released from the hydrogel by breakage of borate ester bonds between CGA and PBA based on high reactive oxygen species (ROS) levels of damaged tissue and exhibited great ROS scavenging capability to regulate inflammation and promote the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the grafted SB as a zwitterionic group could reduce protein adsorption and fibroblast adhesion. Finally, the in vivo experiments revealed that AHBC/PSC hydrogel with good safety and in vivo retention behavior of about 2 weeks, effectively prevented PAA by regulating the inflammatory microenvironment and alleviating the fibrosis process. In brief, the versatile AHBC/PSC hydrogel would provide a more convenient and efficient approach for PAA prevention. Statement of significance Postoperative abdominal adhesion (PAA) widely occurs after surgery and is often accompanied by severe complications. Excessive inflammation and oxidative stress are very crucial for PAA formation. This study provides a ROS-responsive and scavenging hydrogel with suitable mechanical properties, good biocompatibility and biodegradability, and resistance to protein and fibroblast. The antioxidant and anti-inflammatory active ingredient could be responsively released from the hydrogel via triggering by the high ROS levels in the postoperative microenvironment thereby regulating the inflammatory balance. Finally, the hydrogel would effectively regulate the development process of PAA thereby achieving non-adhesion wound healing.
研究领域:
生物材料
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组织工程
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外科研究
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生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fan Su,Chong Zhang,Qianyun Zhang,Yi Shen,Saiqi Li,Jianlin Shi,Ya-Xuan Zhu,Han Lin,Bin He
The sepsis-induced acute lung injury (ALI) still represents one of the leading causes of death in critically ill patients, underscoring the need for novel therapies. Excessive activation of immune cells and damage of reactive oxygen species (ROS) are the main factors that exacerbate lung injury. Here, the multifaceted immunomodulatory nanocomplexes targeting the proinflammatory neutrophilic activation and ROS damage are established. The S100A8/9 inhibitor, ABR2575, is loaded in the nanocomplexes, which effectively blocks the neutrophils-S100A8/A9- toll-like receptors (TLRS)-Inflammasome signaling in ALI. Synergically, the SiH nanosheets are encapsulated together with ABR2575 into the core of poly(lactic- co -glycolic acid) (PLGA) nanosponges, to achieve sustainable hydrogen release for the alleviation of ROS-induced lung tissue injury, and also promote the M2 polarization of macrophages. This novel combination strategy is proven to significantly suppress the infiltration of neutrophils and pro-inflammatory macrophages into the lungs, decrease the activation of neutrophils and pro-inflammatory monocytes in the blood, facilitate the anti-inflammatory polarization of macrophages and monocytes, and reduce the expression of pro-inflammatory cytokines in both the lung and blood circulation, all of which alleviate the lung injuries in preclinical murine ALI models. The current investigations offer a novel nanomedicine for the treatment of ALI with great potential in clinical invention.
研究领域:
纳米医学
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免疫学
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肺科学
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药理学
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重症医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Qingfa Tang,Yao Chen,Yusheng Zhang,Kewei Wang,Li Liu,Dongmei Pan,Qiang Liu,Cuiping Jiang
Tanshinone IIA (TS-IIA) and salvianic acid A (SAA) are the main pharmacological active constituents of Danshen, which exhibit potent effects on atherosclerosis. A combination of TS-IIA and SAA might exert a synergistic antiatherosclerotic effect. However, the opposite solubility profiles of TS-IIA and SAA might lead to difficulty in achieving a synergistic combined effect of the two active components. Therefore, in this work, we fabricated a ROS-responsive prodrug micelle for the codelivery of TS-IIA and SAA (TS-IIA-PM) by self-assembling amphiphilic block copolymer PEG5000-SAA/PLA10000-APBA. The amphiphilic polymer was characterized by 1H NMR, FTIR, and alizarin red S competition tests. The ROS responsiveness of TS-IIA-PM was evidenced by time-course monitoring of particle size and morphology changes and drug release behavior in the presence of 1 mM H2O2. We found TS-IIA-PM was stable according to its critical micelle concentration and the unchanged particle sizes in 10% FBS for 7 days. The results of in vitro and in vivo tests revealed that TS-IIA-PM was safe and biocompatible. Furthermore, it was observed that TS-IIA and prodrug micelle could produce synergistic antiatherosclerotic effect based on the results of the antioxidant study, which was further confirmed by a series of pharmocodynamics studies, such as in vitro DiI-oxLDL uptake study, oil red O staining, cholesterol efflux study, inflammatory cytokine analysis, in vivo CD68 immunostaining, and lipid disposition staining studies. Collectively, TS-IIA-PM holds great potential for the safe and efficient codelivery of TS-IIA and SAA for synergistic antiatherosclerosis.
研究领域:
药学
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纳米技术
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心血管疾病
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2021
·
IF 9.776
Jie Yang,Siyu Ma,Rui Xu,Yawen Wei,Jun Zhang,Tiantian Zuo,Zhihua Wang,Huizi Deng,Ning Yang,Qi Shen
Antitumor immunotherapy is limited by low tumor immunogenicity and immunosuppressive microenvironment (TIME), which could be improved by “ROS-ferroptosis-glycolysis regulation” strategy. Herein, a cancer cell membrane coated metal organic framework (MOF) loading with glucose oxidase (GOx) and doxorubicin (DOX) was constructed (denoted as mFe(SS)/DG). Benefiting from the homotypic targeting of cancer cell membrane, the nanoplatform effectively accumulated in tumors. mFe(SS)/DG based on coordination between Fe 3+ and disulfide-bearing ligand scavenged GSH and downregulated glutathione peroxide 4 (GPX4) to trigger ferroptosis. GOx catalyzed glucose to generate abundant H 2 O 2 for enhancing Fenton reaction, resulting in excessive ROS in tumors. The ROS burst simultaneously promoted ferroptosis and inhibited glycolysis. Ferroptosis combined with DOX induced immunogenic cell death (ICD) and released tumor antigens to initiate antitumor immunity. Glycolysis repression remodeled TIME by decreasing lactate to solidify and boost the antitumor immunity. The smart biomimetic nanoplatform integrates tumor metabolism and immunity based on ROS-ferroptosis-glycolysis regulation, providing a potential anti-tumor strategy.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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生物化学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Qin Wang,Xuedan Nie,Yifan Song,Haiyan Qiu,Liting Chen,He Zhu,Xueli Zhang,Mengru Yang,Xiaohui Xu,Peidan Chen,Chao Zhang,Jia Xu,Yeping Ren,Wenting Shang
Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn3O4 nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn3O4 NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn3O4 NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn3O4 protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.
研究领域:
纳米医学
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药理学
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免疫学
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肾脏生理学
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氧化应激研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Meng Han,Jincheng Tang,Haiyue Zhao,Yachao Sheng,Ziang Li,Wenxiao Shi,Jiahao Wang,Chao Ma,Kun Xi,Yong Gu,Liang Chen
Management of dura tear during spine surgery remain challenging due to the complex focal environment. Current sealants could hardly independently repair dura tear while simultaneously regulate epidural inflammation and fibrosis induced by oxidative stress. A bioadhesive hydrogel sealant with active reactive oxygen species (ROS)-scavenging potential for suppression of epidural inflammation and fibrosis was designed to provide a versatile tool for spine surgeon. In order to achieve such goal, tannic acid-functionalized black phosphorus nanosheets with better ambient stability were incorporated and integrated into network of hydrogel sealant. Such integration was found to bring improved mechanical strength and sealing performance as evidenced by higher burst pressure and effective sealing of dura tear under in vivo environment. Moreover, instead of merely acting as a physical sealing barrier, the hydrogel sealant was also found with active ROS-scavenging capability. Effective inhibition on oxidative stress-mediated epidural inflammation and fibrosis was observed with employment of hydrogel sealant as revealed by both in vitro and in vivo studies. The proposed hydrogel sealant could provide a potential candidate for sealing of dura tear, and may hopefully provide a promising strategy for prevention of epidural fibrosis.
研究领域:
生物医学工程
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材料科学
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神经外科
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药学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Pilong Shi,Yuetong Sha,Xinran Wang,Tao Yang,Jiawei Wu,Jiajun Zhou,Kai Liu,Xue Guan,Song Wang,Yongsheng Liu,Jingquan Gao,Hongli Sun,Tao Ban,Yonggang Cao
Purpose Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2.
研究领域:
心血管疾病
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纳米技术
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药理学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2022
·
IF 6.819
Zhan Yujuan,Chen Qiugu,Song Yue,Wei Xianli,Zhao Tingxiu,Chen Bonan,Li Chengxi,Zhang Wenbo,Jiang Yanjun,Tan Yuhui,Du Biaoyan,Xiao Jianyong,Wang Kun
Autophagy is typically activated in cancer cells as a rescue strategy in response to cellular stress (e.g., chemotherapy). Herein, we found that Berbamine Hydrochloride (Ber) can act as an effective inhibitor of the late stage of autophagic flux, thereby potentiating the killing effect of chemotherapy agents. Lung carcinoma cells exposed to Ber exhibited increased autophagosomes, marked by LC3-II upregulation. The increased level of p62 after Ber treatment indicated that the autophagic flux was blocked at the late stage. The lysosome staining assay and cathepsin maturation detection indicated impaired lysosomal acidification. We found that Nox2 exhibited intensified co-localization with lysosomes in Ber-treated cells. Nox2 is a key enzyme for superoxide anion production capable of transferring electrons into the lysosomal lumen, thereby neutralizing the inner protons; this might explain the aberrant acidification. This hypothesis is further supported by the observed reversal of lysosomal cathepsin maturation by Nox2 inhibitors. Finally, Ber combined with cisplatin exhibited a synergistic killing effect on lung carcinoma cells. Further data suggested that lung carcinoma cells co-treated with Ber and cisplatin accumulated excessive reactive oxygen species (ROS), which typically activated MAPK-mediated mitochondria-dependent apoptosis. The enhanced anti-cancer effect of Ber combined with cisplatin was also confirmed in an in vivo xenograft mouse model. These findings indicate that Ber might be a promising adjuvant for enhancing the cancer cell killing effect of chemotherapy via the inhibition of autophagy. In this process, Nox2 might be a significant mediator of Ber-induced aberrant lysosomal acidification. Graphical abstract
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Fangyuan Jing,Yuda Zhu,Fan Li,Yilan Wang,Xiuxian Yu,Kun Zhang,Guang Xin,Wen Huang
Acute pancreatitis (AP) is a life-threatening inflammatory disease of the pancreas. When AP occurs, macrophages are recruited and stimulated to pro-inflammatory M1 phenotype, releasing pro-inflammatory factors and reactive oxygen species (ROS). Therefore, macrophage polarization is one of the most promising therapeutic strategies for AP therapy. In this study, we designed a chitosan-based inflammation-responsive nanosystem, which successfully integrates ROS scavenging, macrophage polarization and multimodal imaging for AP treatment. Through a convenient hydrothermal method, Ce and Gd bimetallic ions doped CDs (Ce/Gd-CDs) were successfully constructed, which showed excellent ROS scavenging and magnetic resonance imaging (MRI) function. Then, chitosan was employed as an inflammation-responsive carrier for loading with both Ce/Gd-CDs and resveratrol (RES), forming multifunctional therapeutic agent CDs/ [email protected] NPs (CRCS). The pH-sensitive chitosan carriers were able to reduce the biotoxicity of Ce/Gd-CDs and RES and prolong their in vivo circulation time, thus advancing their utilization. Taken together, the in vitro and in vivo studies of CRCS displayed a favorable synergistic potency of ROS scavenging, macrophage polarization and multimodal imaging, significantly reducing AP. Our design expands the biological application of multifunctional nano-enzymes while providing a novel strategy toward constructing microenvironment-responsive therapeutic platforms for inflammatory disease treatment.
研究领域:
纳米技术
·
生物医学工程
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药学
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成像科学
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炎症生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Haifeng Lu,Qi Lu,Hongwu Sun,Zhongkun Wang,Xiang Shi,Yuling Ding,Xiang Ran,Jing Pei,Yubo Pan,Qunlin Zhang
Intracellular reactive oxygen species (ROS) are closely associated with cancer cell types. Therefore, ROS-based pattern recognition is a promising strategy for precise diagnosis of cancer, but such a possibility has never been reported yet. Herein, we proposed an ROS-responsive fluorescent sensor array based on pH-controlled histidine-templated gold nanoclusters (AuNCs@His) to distinguish cancer cell types and their proliferation states. In this strategy, three types of AuNCs@His with diverse fluorescence profiles were first synthesized by only adjusting the pH value. Upon the addition of various ROS, fluorescence quenching of three types of AuNCs@His occurred with different degrees, thereby forming unique optical “fingerprints”, which were well-clustered into several separated groups without overlap by principal component analysis (PCA). The sensing mechanism was attributable to the oxidation of AuNCs@His by ROS, as revealed by X-ray photoemission spectroscopy, Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Based on the ROS-responsive sensing pattern, cancer cell types were successfully differentiated via PCA with 100% accuracy. Additionally, the proposed sensor array exhibited excellent performance in distinguishing the proliferation states of cancer cells, which was supported by the results of the Ki-67 immunohistochemistry assay. Overall, the ROS-responsive fluorescent sensor array can serve as a promising tool for precise diagnosis of cancer, indicating great potential for clinical application.
研究领域:
癌症生物学
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纳米技术
·
分析化学
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生物医学工程
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分子生物学
✓ 已验证
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）