PROCESS SAFETY AND ENVIRONMENTAL PROTECTION
·
2024
·
IF 6.9
Danqing Zheng,Jiehan Duan,Yanlin Wu,Wenbo Dong
As an emerging class of pollutants, microplastics (MPs) coexisting with organic contaminants (OCs) exhibit environmental behaviors that have raised widespread concerns. This study investigated the influence of aged polystyrene microplastics (PSMPs) on the photoconversion of losartan potassium (LSTP) under irradiation. The experimental results indicated that the presence of PSMPs significantly enhanced the photodegradation of LSTP (from 9.11% to 83.32%) and showed a positive linear relationship with the aging degrees. Characterization of PSMPs and quenching experiments revealed that reactive oxygen species (ROS) induced by oxygen-containing groups on the surface of aged PSMPs were responsible for promoting LSTP photodegradation . Singlet oxygen ( 1 O 2 ) dominated and contributed more than 50% with different aging levels of PSMPs involved. Photoconversion products of LSTP were deduced based on density functional theory calculations and liquid chromatography-time of flight-mass spectrometry analysis. Their relative abundance of supported the positive correlation between ROS variations and aging degrees of PSMPs. This study highlights the critical impact of aging MPs on the fate of OCs in the aquatic environment .
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Fangyuan Guo,Yunlong Jiao,Yinzhou Du,Shuai Luo,Weiyong Hong,Qiafan Fu,Aiqin Li,Guoping Wang,Gensheng Yang
Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star -shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Xiaohui Zhang,Zhongliang Nie,Shuang Wang,Yuxi Ma,Dan Han,Ting Hu,Liu Liu,Liying Men,Tao Zhang,Xiaoting Wu,Xu Li,Sheng Hu,Meng Yuan,Liu Liu,Chaoqun Wang,Ping Xu,Limin Xiang,Jiao Liu,Yong Zhang,Dahai Zhu,Hehua Lei,Limin Zhang,Xiangpan Li,Yanxia Zhao,Wei Yan
Radiotherapy reduces the risk of cancer recurrence and death, but the fact that it's accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify that cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles to trigger skeletal muscle weakness upon radiotherapy. Mechanistically, irradiation-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of the SRM protein, facilitating SRM packaging into extracellular vesicles from the primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon radiotherapy, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of radiotherapy-mediated muscle weakness when combined with losartan treatment.
研究领域:
肿瘤学
·
生物化学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Xiaoqing Zhai,Shusen Tang,Fanhu Meng,Jihong Ma,Aimei Li,Xiangyu Zou,Baolong Zhou,Fujun Peng,Jingkun Bai
The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
Acta Biomaterialia
·
2019
·
IF 6.638
Yapei Zhang,Yang Liu,Xuefeng Gao,Xiaomin Li,Xiaoyan Niu,Zhi Yuan,Wei Wang
Tumor tissue presents much denser and stiffer extracellular matrix (ECM), which can hinder the penetration of most nanoparticles (NPs) and contribute to the tumor cell proliferation . Here, NIR-activated losartan was encapsulated in hollow mesoporous prussian blue nanoparticles (HMPBs) to degrade ECM. The results showed that losartan enhanced the penetration of DOX, 1.47% of the injected dose (ID) of DOX reached the tumor tissues, which was 3.00-fold higher than the control group (0.49%). In addition, as the existence of thermo-sensitive lauric acid , (Losartan + DOX)@HMPBs could achieve near “zero drug leakage” during blood circulation, so as to reduce the damage of DOX to normal tissues. Furthermore, the animal experiments proved tumor inhibition ability of (Losartan + DOX)@HMPBs in synergistic of photothermal/chemotherapy, with the tumor growth inhibition rate of 81.3%. Taken together, these findings can be a candidate for developing vectors with enhanced tumor penetration and therapeutic effect in future clinical application. Statement of significance Due to the existence of denser extracellular matrices (ECM), only 0.7% of the administered nanoparticles dose is delivered to tumor, which will limit the tumors’ therapeutic effect. Degradation of ECM can improve the penetration of nanoparticles in tumors. However, no researchers has encapsulated losartan in nanoparticles to degrade ECM. Herein, we developed a NIR induced losartan and DOX co-delivery system based on hollow mesoporous prussian blue nanoparticles (HMPBs) to degrade ECM and improve the penetration of nanoparticles in tumors. The prepared nanoparticles can also acheive near “zero drug leakage” during blood circulation and “fixed-point drug release” in tumor, so as to reduce the damage of DOX to normal tissues. We believe the prepared nanoparticles provide a new platform for cancer treatment.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TRIBOLOGY INTERNATIONAL
·
2025
·
IF 6.9
Yi Zhou,Min Zhong,Guoxin Xie,Meirong Yi,Xiaobing Li,Jianfeng Chen,Wenhu Xu
Cobalt (Co) as an emerging interconnect solution for integrated circuits (ICs) is prone to corrosion during chemical mechanical polishing (CMP). However, traditional inhibitors are toxic and inefficient, making the development of non-toxic and highly efficient inhibitors urgent. This study reports for the first time that the antihypertensive drug Losartan exhibits excellent performance in balancing corrosion protection and polishing efficiency in Co CMP processes. Polishing experiments and Atomic Force Microscope (AFM) tests reveal that Losartan enhances the material removal rate (MRR) while improving surface integrity relative to Benztriazole (BTA). Electrochemical tests, adsorption isotherms, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) confirm that Losartan's comprehensive performance as a new organic inhibitor surpasses that of BTA. Energy dispersive spectroscopy (EDS) results indicate that Losartan forms a dense protective adsorption film on the Co surface. Density functional theory (DFT) reveals Losartan’s multisite adsorption on the Co surface through various sites of nitrogen, oxygen, and chlorine atoms. It theoretically explains that its corrosion inhibition effect is superior to BTA. This study provides reference for choosing green and effective corrosion inhibitor for Co CMP.
研究领域:
材料科学
·
微电子制造
·
表面工程
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电化学
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计算化学
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半导体工艺
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Irfan Ijaz,Aysha Bukhari,Ezaz Gilani,Ammara Nazir,Hina Zain,Attia Shaheen,Mohammed Rafi Shaik,Mujeeb Khan,Mohamed E. Assal
A rising quantity of drugs has been discharged into the aquatic environment, posing a substantial hazard to public health. In the current work, a novel hydrogel (i.Carr@Bent@PTC), comprised of iota-carrageenan, bentonite, and 4-phenyl-3-thiosemicarbazide, was successfully prepared. The introduction of 4-phenyl-3-thiosemicarbazide and bentonite in iota-carrageenan significantly increased the mechanical strength of iota-carrageenan hydrogel and improved its degree of swelling, which can be attributed to the hydrophilic properties of PTC and Bent. The recorded contact angle was 70.8°, 59.1°, 53.9°, and 34.6° for pristine i.Carr, i.Carr@Bent, and i.Carr@Bent@PTC, respectively. The low contact angle measurement of the Bent and PTC loaded-i.Carr hydrogel was attributed to the hydrophilic Bent and PTC. The ternary i.Carr@Bent@PTC hydrogel demonstrated broad pH adaptability and excellent adsorption capacities for sulfamethoxazole (SMX) and losartan potassium (LP), i.e., 467.61 mg. g −1 and 274.43 mg. g −1 at 298.15 K, respectively. The pseudo-first-order (PSO) model provided a better fit for the adsorption kinetics . The adsorption of SMX and LP can be better explained by employing the Sips and Langmuir isotherm models. As revealed by XPS and FTIR investigations, π-π stacking, complexation, electrostatic interaction , and hydrogen bonding were primarily involved in the adsorption mechanisms.
研究领域:
环境科学
·
材料科学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HYPERTENSION RESEARCH
·
2022
·Vol. 46
·期 4
·972-983
·
IF 5.528
Shen Yuchen,Wang Zhenfeng,Su Lixin,Zheng Lianzhou,Han Yifeng,Jiao Xiaohui,Fan Xindong,Wang Deming
This study aimed to examine whether the administration of losartan can prevent acute elevation of pulmonary arterial pressure (AEPAP) induced by endovascular ethanol injection and to assess its related mechanisms. Male swine were selected and performed with absolute ethanol endovascular injection. Saline was used as the negative control. Losartan was administered preoperatively. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP) and heart rate (HR) were monitored during operations. Venous plasma and pulmonary artery (PA) tissue were harvested for analyses. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry were conducted to evaluate histopathology. Ethanol injection elevated PAP in swine. The concentration of RAS ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R ( P < 0.01, 95% CI: 0.251–1.006), not AT2R increased in PA. Losartan failed to inhibit AEPAP after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling. The P38 MAPK was activated after ethanol injection and could be inhibited by losartan ( P < 0.01, 95% CI: −0.391 to −0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol.
Mechanism diagram of endovascular ethanol injection-induced acute elevation of pulmonary arterial pressure (AEPAP) partially prevented by losartan. RAS: Renin–angiotensin system; AGT: angiotensinogen; Ang I: angiotensin I; ACE: angiotensin I converting enzyme; Ang II: angiotensin II. AT1R: angiotensin II type 1 receptor. NOX2: NADPH oxidase 2. PA: pulmonary artery.
研究领域:
药理学
·
心血管研究
·
动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Rui Ni,Lele Huang,Zhen Li,Wenli Zhang,Yajie Wang,Yan Shen,Jianxin Wang,Weigen Lu
Purpose To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug. Methods A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG 5% ). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging. Results ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the un-transformable preparations in three-dimensional (3D) tumor spheroids. Furthermore, synergetic penetrating enhancement was achieved by LST-loaded transformable LPNs in 4T1 and fibroblast cell mixed 3D tumor spheroids. The improved tumor penetration of LST-loaded transformable LPNs was observed in vivo, which could be due to their collagen inhibiting and size/shape transformable effect. Due to their enhanced penetrability, LST and PTX-loaded transformable LPNs demonstrated significant in vivo antitumor efficacy in comparison to other preparations. Conclusion The results confirmed the efficacy of M/LST-Lip/PTX-PEG 5% in tumor targeting, collagen inhibition in TME, and enhanced tumor penetration. This novel drug delivery system can therefore play a substantial role in improving the therapeutic efficacy of antitumor drugs combined with TME-improving agents.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Huilin Zhang,Yiwei Zhang,Haili Hu,Wenqin Yang,Xue Xia,Lei Lei,Ruyi Lin,Jiamei Li,Yuan Li,Huile Gao
Tumor vaccine is a promising cancer treatment modality, however, the convenient antigens loading in vivo and efficient delivery of vaccines to lymph nodes (LNs) still remain a formidable challenge. Herein, an in situ nanovaccine strategy targeting LNs to induce powerful antitumor immune responses by converting the primary tumor into whole-cell antigens and then delivering these antigens and nanoadjuvants simultaneously to LNs is proposed. The in situ nanovaccine is based on a hydrogel system, which loaded with doxorubicin (DOX) and nanoadjuvant CpG-P-ss-M. The gel system exhibits ROS-responsive release of DOX and CpG-P-ss-M, generating abundant in situ storage of whole-cell tumor antigens. CpG-P-ss-M adsorbs tumor antigens through the positive surface charge and achieves charge reversal, forming small-sized and negatively charged tumor vaccines in situ, which are then primed to LNs. Eventually, the tumor vaccine promotes antigens uptake by dendritic cells (DCs), maturation of DCs, and proliferation of T cells. Moreover, the vaccine combined with anti-CTLA4 antibody and losartan inhibits tumor growth by 50%, significantly increasing the percentage of splenic cytotoxic T cells (CTLs), and generating tumor-specific immune responses. Overall, the treatment effectively inhibits primary tumor growth and induces tumor-specific immune response. This study provides a scalable strategy for in situ tumor vaccination.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Hou Xiaodong,Shen Yuting,Huang Bin,Li Qiuyan,Li Shaoyue,Jiang Tingting,Shan Xuexia,Xu Weichen,Liu Shuo,Wu Shengbo,Zhao De,Zhu Anqi,Sun Liping,Xu Huixiong,Yue Wenwen
Preclinical studies demonstrating high cure rates with PD1/PD-L1 combinations have led to numerous clinical trials, but emerging results are disappointing. These combined immunotherapies are commonly employed for patients with refractory tumors following prior treatment with cytotoxic agents. Here, we uncovered that the post-chemotherapy tumor presents a unique mechanical microenvironment characterized by an altered extracellular matrix (ECM) elasticity and increased stiffness, which facilitate the development of aggressive tumor phenotypes and confer resistance to checkpoint blocking therapy. As thus, we rationally designed an in situ nanocomposite hydrogel system, LOS&FeOX@Gel, which enabled effective and specific delivery of the therapeutic payloads (losartan [LOS] and oxaliplatin [OX]) into tumor. We demonstrate that sustained release of LOS effectively remodels the tumor mechanical microenvironment (TMM) by reducing ECM deposition and its associated “solid stress”, thereby augmenting the efficacy of OX and its immunological effects. Importantly, this hydrogel system greatly sensitized post-chemotherapy tumor to checkpoint blocking therapy, showing synergistic therapeutic effects against cancer metastasis. Our study provides mechanistic insights and preclinical rationale for modulating TMM as a potential neoadjuvant regimen for tumor to optimize the benefits of chemo-immunotherapy, which lays the groundwork for leveraging “mechanical-immunoengineering” strategies to combat refractory tumors. Graphical Abstract
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 6
·1658-1668
·
IF 6.183
Zhengjie Zhou,Yang Yan,Qiang Zhang,Yiyun Cheng
An abnormal tumor growth induces solid stress in tumors, thus reducing blood perfusion. As a result, the impaired blood perfusion, with dense interstitial matrix in tumors significantly reduces the penetration and efficacy of nanotherapeutics. In this study, we have developed a losartan-loaded polydopamine nanoparticle (PLST) for the enhanced delivery of nanoparticles to tumors and improved photothermal cancer therapy. Losartan, an angiotensin inhibitor, is also able to alleviate the solid stress in tumors. It was laden on polydopamine nanoparticles via π–π stacking and was released upon tumor extracellular acidity. PLST reduced collagen production in vitro along with the lowered expression of profibrotic factors of TGF-β1, CCN2, and TIMP-1. The in vivo studies reveal that PLST reduced solid stress in tumors, and the amount of PLST accumulated in tumors was enhanced. The efficiency of the photothermal ablation of tumors was significantly enhanced by using PLST.
研究领域:
癌症治疗
·
纳米技术
·
药学科学
·
生物医学工程
✓ 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）