Nano-Micro Letters
·
2024
·Vol. 16
·期 1
·1-21
·
IF 31.6
Zhou Xi,Zhou Quan,He Zhaozhi,Xiao Yi,Liu Yan,Huang Zhuohang,Sun Yaoji,Wang Jiawei,Zhao Zhengdong,Liu Xiaozhou,Zhou Bin,Ren Lei,Sun Yu,Chen Zhiwei,Zhang Xingcai
The innovation of this work mainly lies in the auto-regulation of reactive oxygen species (ROS) balance effective by combination of ROS antibacterial and ROS scavenging anti-inflammatory functions with a core–shell nanoplatform (CeO 2 @ZIF-8/Au), which can not only achieve high antibacterial efficiency, but also promote wound healing, and provide a new idea for the nano-catalytic system in the field of wound healing of bacterial infection.
研究领域:
纳米技术
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材料科学
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生物医学工程
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Ruoxin Tu,Yining Wang,Ru Xu,Shusheng Wang,Jiabin Cai,Lin Sun,Pengfei Gao
Despite therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While dihydrotanshinone I (DHT) shows promising anticancer potential, its molecular mechanisms in HCC remain unexplored. Here, we unveil a novel chemokine (C-C Motif) receptor 5(CCR5)-mediated regulatory network targeted by DHT in HCC treatment. This study identifies CCR5 as a crucial survival factor in HCC, uncovers a novel CCR5-Nuclear factor erythroid 2-related factor 2(NRF2) regulatory axis, and reveals a dual-targeting mechanism of DHT through direct CCR5 inhibition and Reactive oxygen species(ROS)-dependent cell death induction, validating its therapeutic efficacy by disrupting redox homeostasis. This study uncovers a novel CCR5-ROS-NRF2 signaling axis in HCC and establishes DHT as a promising therapeutic agent through its unique targeting mechanism. These findings provide new insights into HCC pathogenesis and present an innovative therapeutic strategy for HCC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Shanshan Liu,Bingnan Wang,Yuewen Yu,Yubo Liu,Zeyan Zhuang,Zujin Zhao,Guangxue Feng,Anjun Qin,Ben Zhong Tang
Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregation-induced emission (AIE) photosensitizers for photodynamic treatment of drug-resistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant CTBZPyI exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers CTBZPyI with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a MRSA-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.
研究领域:
光动力治疗
·
微生物学
·
药剂学
·
传染病学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Qiyi Zhu,Xiaofeng Zhu,Ning Yang,Yuxi Duan,Yuanyuan Wang,Xiaoyu Liu,Di Zhao,Haiyan Fan,Lijie Chen
Root-knot nematodes ( Meloidogyne incognita ) present a significant threat to global agriculture, and the development of multi-drug resistance in these nematodes exacerbates this problem. Benzothiazole, a heterocyclic compound has been reported as a potential nematicide, however, its mode of action is not fully understood. This study aims to elucidate the nematicidal mechanism of benzothiazole against M. incognita . In the toxicity assays, benzothiazole exhibited rapid and effective nematocidal activity, significantly compromising egg masses and inhibiting egg hatching while killing newly hatched second-stage juveniles (J2s) of M. incognita . Microscopic observations revealed that after 48 h of incubation, a marked reduction in protein and carbohydrate levels within the J2s was observed. Notably, benzothiazole at a concentration of 14 mmol/L significantly inhibits glutathione S-transferase (GST) enzyme activity, leading to the accumulation of reactive oxygen species (ROS), ultimately resulting in rapid nematode death. Molecular docking and dynamics simulations demonstrated that benzothiazole forms a stable complex with GST, thereby disrupting its antioxidant function. Furthermore, in pot experiments, benzothiazole effectively reduced the gall formations of M. incognita on tomato roots. Overall, this novel inhibitory mechanism of glutathione S-transferase (GST) differs from that of the neurotoxicant abamectin, which targets glutamate-gated chloride channels (GluCl). This mechanism holds significant promise for the development of environmentally friendly nematicides. It offers a potential solution to the growing problem of multidrug resistance in root-knot nematodes and could help mitigate the substantial economic losses caused by these pests in global agriculture.
研究领域:
农业科学
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害虫防治
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生物化学
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线虫学
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植物病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2025
·
IF 3.6
Sunqi Yu,Siyuan Chen,Tianrui Tong,Yunfeng Yan,Qi Shuai
Micelle-based drug delivery systems (DDS) have emerged as a promising solution to address challenges associated with the in vivo delivery of hydrophobic anticancer chemotherapeutics. However, micelles still encounter issues such as drug pre-leakage and poor stability in physiological conditions. To overcome these limitations, we developed a core-cross-linking strategy utilizing amphiphilic copolymers, mPEG- b- P(AVL- co -LA) (mPPAL), functionalized with phenylboronic acid (PBA), and catechol by CuAAc “click” chemistry, respectively. These copolymers self-assembled into core-cross-linked micelles (CLMs), featuring boronic ester bonds, which were characterized through a series of evaluations. The CLMs exhibited a rational particle size, uniform morphology, low critical micelle concentration (CMC), high PTX loading capacity, and excellent stability. Two promising micelles, CLM1 and CLM3, were identified, and their responsiveness to acidic pH and elevated levels of ROS was confirmed to enable controlled PTX release. The results of MTT assay and hemolytic analysis demonstrated high biocompatibility and potential in vivo application of these selected CLMs. The anticancer efficacy of the selected PTX-CLMs was further validated through MTT assay and 3D tumor spheroid studies. Fluorescence microscopy and flow cytometry demonstrated rapid intracellular uptake of the CLMs. In vivo biodistribution studies demonstrated successful accumulation in the targeted tumor tissue. These findings suggest that the boronic ester-based CLMs developed in this study are a promising nanocarrier for effective PTX delivery. Graphical Phenylboronic acid (PBA) and catechol-modified amphiphilic copolymers (mPPAL@R) were synthesized via ring-opening polymerization followed by CuAAc click chemistry. These copolymers were employed to construct pH- and ROS-dual-responsive micelles with boronic ester core-crosslinking. A series of in vitro and in vivo experiments were conducted to evaluate PTX-loaded micelles, demonstrating their significant potential for effective PTX delivery.
研究领域:
药剂学
·
肿瘤学
·
材料科学
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产品关联
DOI
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2023
·
IF 4.3
Shiliang Zhu,Ke Li,Shuai Qin,Jianguo Lin,Ling Qiu
Traditional photodynamic therapy (PDT) suffers from poor tissue penetration due to using external light as excitation source. Cerenkov radiation (CR) from radionuclides can serve as an internal light source to activate photosensitizers inside lesion tissues. Using CR instead of external light in PDT is thought to be an effective way to overcome the shortcoming of traditional PDT. However, the weakness of CR emission limits the outcomes of CR-induced PDT (CR-PDT). We anticipated that CR-induced combined therapy could effectively enhance the therapeutic outcome of CR-PDT. Herein, a ROS-responsive Chemo-PDT agent ( TTC ) was synthesized by conjugation of tetraphenylporphyrin (photosensitizer) with camptothecin (chemotherapeutic drug) through a ROS-cleavable thioketal linker. Under activation by CR emission from gallium-68 ( 68 Ga), the porphyrin moiety could generate ROS , which then cleaves the thioketal linker to induce the subsequent release of CPT. Using [ 68 Ga]Ga-NOTA-Nb109 as an intracellular CR emitter, in comparison with its non-cleavable analogue ( TUC ) only displaying phototoxicity, TTC exhibited much higher cytotoxicity toward A375-hPD-L1 cells due to its combined effect of PDT and chemotherapy. Our work presents a new strategy to use ROS-responsive Chemo-PDT agent to improve the outcomes of CR-PDT.
研究领域:
放射治疗
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癌症治疗
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核医学
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Min Tan,Jing Zeng,Fu-Zhong Zhang,Ye-Tao Zhang,Hongli Li,Shu-Ting Fan,Jia-Xin Wang,Minglong Yuan,Bang-Jing Li,Sheng Zhang
Slow healing of wounds induces great pain in diabetic patients. However, developing new approaches to promote diabetic wound healing is still one of the toughest challenges in the medical field. Here, we constructed a new double-layer hydrogel to effectively regulate reactive oxygen species (ROS) on the wound and promote diabetic wound healing. The inner layer contains glucose oxidase (Gox), ferrocene-modified quaternary ammonium chitosan (Fc-QCs), and poly(β-cyclodextrin) (Pβ-CD), which is used to generate hydroxyl radicals (•OH) for antibacterial in the early stage of wound healing and collapses gradually. The outer layer is composed of gelatin and dopamine. In the later stage of wound healing, the outer layer contacts the skin, which is beneficial for ROS clearance on the wound. Antibacterial, ROS scavenging, and wound healing experiments have shown that the double-layer hydrogel possesses two-stage ROS regulating properties for programmed diabetic wound healing. In conclusion, it will be one of the most potential dressings for treating diabetic wounds in the future.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Qingqing Pan,Xin Deng,Wenxia Gao,Jing Chang,Yuji Pu,Bin He
With the utilization of high concentration reactive oxygen species (ROS) in tumor microenvironment, PEG-doxorubicin (PEG-DOX) prodrug was synthesized via a thioketal moiety as the linker, which was ROS cleavable to trigger DOX release from the self-assembled prodrug nanoparticles. The in vitro ROS sensitivity of prodrug nanoparticles (NPs) was investigated in Fenton agent and H 2 O 2 , and the disassembly of NPs was more sensitive to Fenton reagent. After internalized in HepG2 cells via endocytosis, the cellular ROS consuming test revealed intracellular DOX release. The pharmacokinetics and biodistribution study demonstrated that the in vivo elimination of NPs was significantly improved and the NPs were passively targeted to tumor tissues via EPR effect. The ROS-responsive prodrug NPs exhibited excellent antitumor activity in HepG2 tumor-bearing nude mice, remarkably induced tumor cells apoptosis and reduced the systemic toxicity of DOX. Our study revealed the ROS responsive prodrug nanoparticle is an effective strategy to fabricate nanomedicine for cancer chemotherapy.
研究领域:
药物递送系统
·
肿瘤学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xiaoting Yu,Yannan Chen,Mingqian Tan
The controlled release of antioxidant substances at the intestinal oxidative damage site is crucial for alleviating intestine-related diseases. Herein, the novel ROS-responsive carrier was synthesized through simple amidation reaction between carboxymethyl chitosan (CMC) and methionine (Met), a natural organic compound containing ROS-responsive linkages (thioether). Initially, astaxanthin (AXT) nanoparticles (AXT 2 @CMT) with excellent stability and drug loading capacity (39.68 ± 0.23 μg/mL) were prepared by optimizing various reaction conditions. In the simulated high-concentration ROS environment of the intestine, CMT achieved a transition from hydrophobic groups (thioether) into hydrophilic groups (sulfone), which was conducive to the controlled release of AXT. In vitro cell experiments revealed that AXT 2 @CMT could effectively alleviate the oxidative damage in intestinal epithelioid cell line No. 6 (IEC-6 cell) caused by H 2 O 2 . This study achieved a straightforward preparation of ROS-responsive nanocarrier through food ingredients, offering a theoretical foundation for the controlled release of AXT at the intestinal oxidative damage site.
研究领域:
纳米技术
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Jie Li,Chunyang Sun,Wei Tao,Ziyang Cao,Haisheng Qian,Xianzhu Yang,Jun Wang
Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo . However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NP Ce6&PTX to circumvent the aforementioned challenge. The TK-NP Ce6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d, l -lactic acid) (PEG- TK -PLA). We demonstrated that the high PEGylation of TK-NP Ce6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time . At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ , which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Fiber Materials
·
2022
·Vol. 4
·期 4
·894-907
·
IF 12.958
Huang Yiqian,Du Zhiyun,Li Ke,Jing Wei,Wei Pengfei,Zhao Bo,Yu Yingjie,Cai Qing,Yang Xiaoping
Bone defects are always accompanied by inflammation due to excessive reactive oxygen species (ROS) in injured regions, which greatly impedes the regeneration of bone tissues. Although many conductive polymers have been developed to scavenge ROS, they are typically non-degradable under physiological conditions, making them unsuitable for in vivo applications. Biodegradable polyorganophosphazenes (POPPs) may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization. Herein, a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid) (PLGA) in regenerating bone tissues. To conduct in vitro and in vivo evaluations, three kinds of electrospun nanofibrous meshes were prepared: PLGA, PLGA/PATGP blend, and PLGA/PATGP core–shell nanofibers. Among them, PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS, promoting osteogenic differentiation, and accelerating neo-bone formation. The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix. Therefore, the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering. Additionally, the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials, without phase separation or difficulty of increasing the molecular weights of POPPs. Graphical abstract
研究领域:
生物材料
·
组织工程
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Oncology
·
2023
·
IF 4.7
Hao Yin,Xingyan Fu,Hanyu Gao,Han Gao,Yannan Ma,Xitong Chen,Xueqi Zhang,Shan-Shan Du,Yun-Kun Qi
Liver cancer is the third leading cause of cancer-associated mortality globally, and >830,000 patients with liver cancer undergoing treatment succumbed to the disease in 2020, which indicates the urgent need to develop a more effective anti-liver cancer drug. In our previous study, nucleus-targeting hybrid peptides obtained from the fusion of LTX-315 and the rhodamine B group possessed potent anti-adherent cancer cell activity. Hybrid peptides accumulated in the cell nucleus and damaged the nuclear membrane, resulting in the transfer of reactive oxygen species (ROS) from the cytoplasm to the nucleus and the induction of apoptosis. However, the source of the high concentration of ROS within the cytoplasm is unclear. Moreover, although our previous study demonstrated that hybrid peptides possessed potent anticancer activity against adherent cancer cells, their efficacy on liver cancer remained unexplored. The current study found that the hybrid peptide NTP-217 killed liver cancer cells after 4-h treatment with a half-maximal inhibitory concentration of 14.6-45.7 μM. NTP-217 could stably accumulate in the liver tumor tissue and markedly inhibited liver tumor growth in mice. Furthermore, NTP-217 destroyed mitochondria and induced the leakage of mitochondrial contents, resulting in the generation of a substantial quantity of ROS. Unlike the apoptosis induced by 24 h of treatment by NTP-217, 4 h of treatment caused ROS-mediated necrotic cell death. These findings suggested that short-time treatment with hybrid peptides could trigger ROS-mediated rapid necrosis in liver cancer cells, and provided a basis for the future development of hybrid peptides as anti-liver cancer agents.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子