LANGMUIR
·
2020
·
IF 3.557
Qicheng Zhang,Zeqing Li,Ming Zhang,Wentao Wang,Jian Shen,Ziqiu Ye,Ninglin Zhou
Postoperative wound repair of solid tumors resection, which is afflicted by the complex tumor microenvironment (TME) and associated with the bacterial infection, is worsening and demands prompt solutions. Meanwhile, the tumor recurrence is frequently seen during the subsequent treatment due to intraoperative bleeding. For effective postoperative cancer therapy, nanoscale carriers occur as innovative and sensitive tools for monitoring the wound state, avoiding bacterial infection, and restraining tumor recurrence. Herein, a multifunctional sodium alginate (SA) hydrogel immobilizing hemoglobin (Hb) and pH-sensitive fluorescent changing carbon quantum dots (CQDs) is rationally designed. The multifunctionalization of obtained alginate@hemoglobin@CQDs hydrogel (SA@Hb@CQDs) simultaneously consists of detection, hemostasis, and chemodynamic therapy (CDT) with monitoring of wound pH based on CQDs, stanching triggered from SA hydrogel, and Fenton reaction induced by Hb. We demonstrated that SA@Hb@CQDs can stop bleeding quickly, collect wound status information in real-time, and avert bacterial infection as well as inhibit local tumor recurrence effectively. Therefore, our work provides a promising combination approach for postoperative tumor therapy.
研究领域:
生物材料
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纳米技术
·
生物医学工程
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癌症治疗
·
伤口愈合
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2020
·
IF 3.693
Niu Weina,Wang Jianguo,Wang Qinyao,Shen Jianjun
Ovarian cancer is a gynecological cancer from which it is difficult to be completely cured. It is common to use regimens as an effective treatment for ovarian cancer, but these inevitably bring serious side effects. New treatment strategies and special drugs are needed to improve the prognosis of patients. Celastrol is a natural product, isolated from traditional medicine, that has been proven to be curative for inflammation and cancers. However, the non-targeting and low solubility of celastrol limit its clinical application. We prepared celastrol-loaded nanoparticles for the efficient treatment of ovarian cancer via oxidative stress amplification. In this work, a tumor-targeted, ROS-sensitive nanoparticle was designed, synthesized, and assembled into a drug delivery system that used celastrol. Folic acid (FA) groups on the surface of nanoparticles guide them to actively target the surface of the tumor cell membrane. Thioketal (TK) bonds in nanoparticles can be oxidized and broken into -SH within the ROS level of tumor tissues, which causes the breaking of the PEG hydrophilic shell layer of nanoparticles and promotes the release of celastrol. The released celastrol further stimulated the production of ROS and amplified the intracellular ROS level to promote the apoptosis of tumor cells, thus achieving a therapeutic effect on the celastrol treated ovarian cancer.
研究领域:
肿瘤学
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药学
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纳米技术
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2021
·Vol. 12
·期 16
·2397-2403
·
IF 5.582
Huan-Huan Ding,Mu-Han Zhao,Le Zhai,Jian-Bin Zhen,Le-Yun Sun,Jia-Zhu Chigan,Cheng Chen,Jia-Qi Li,Han Gao,Ke-Wu Yang
The drug resistance caused due to the overuse of antibiotics has grown into an emerging threat. It is urgent to develop novel strategies to combat bacterial resistance. In this work, a quinine-based quaternized polymer with amphiphilicity (QMTA) was prepared by free-radical copolymerization of quinine and (2-methacryloyloxyethyl) trimethyl ammonium chloride (MTA). Biological activity assays revealed that the polymer sterilized the drug-resistant Gram-negative E. coli and non-resistant Gram-positive bacteria B. subtilis, exhibiting a MIC value of 2 μg mL−1 and a bactericidal rate of more than 95%. Most importantly, both E. coli and B. subtilis treated with the polymer didn't develop resistance even after their 16th passages. Also, the polymer has low toxicity at a dose of up to 128 μg mL−1. The mechanism studies through SEM and 3D-SIM images, fluorescence staining and membrane potential determination reveal that the positively charged QMTA initially concentrates on the surface of bacteria by electrostatic adsorption, changes the membrane potential, binds to the bacteria by its quinine chain, and destroys the membrane structure of the bacteria. This study provides a potential approach through the existing drug to develop new bactericidal reagent/polymer materials without resistance.
研究领域:
聚合物化学
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微生物学
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材料科学
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药剂学
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产品关联
DOI
高影响因子
Inorganic Chemistry Frontiers
·
2021
·Vol. 8
·期 10
·2624-2633
·
IF 6.569
Man Zou,Yajie Zhao,Binbin Ding,Fan Jiang,Yeqing Chen,Ping'an Ma,Jun Lin
The generation of reactive oxygen species (ROS) is often limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME) and the penetration depth of visible light. In view of this, we designed biodegradable Cu/ZIF-8 shell-coated lanthanide-doped nanoparticles and loaded with a photosensitizer (Rose Bengal), and fabricated a NIR-triggered nanocomposite NaYF4:20%Yb, 2%Er@Cu/ZIF-8/RB@F127 (UCZRF) for the synergistic treatment of CDT and PDT. Interestingly, the UCZRF nanostructures can specifically release RB and Cu2+ in the acidic tumor microenvironment (TME). Cu2+ depletes GSH to effectively change the amount of ROS produced by RB under 980 nm laser irradiation, and Cu+ from the reduction reaction of GSH reacts with excess hydrogen peroxide (H2O2) in the TME to generate hydroxyl radicals (⋅OH) with high oxidation activity. In such a simple nanosystem, we enhance the anti-tumor effect of CDT and PDT by improving the efficiency of ROS generation.
研究领域:
纳米医学
·
肿瘤治疗
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材料科学
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生物化学
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产品关联
DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2021
·
IF 4.219
Qiang Zheng,Yuan Zhang,Zheng Zhao,Haitao Shen,Hongyu Zhao,Min Zhao
Isorhynchophylline (IRN) is an alkaloid with anti-inflammatory and anti-oxidative activities in cardiovascular and brain diseases, but its role in paraquat (PQ)-induced acute kidney injury (AKI) is yet unknown. The model of PQ-induced AKI in rats was established by intraperitoneal injection of PQ (25 mg/kg). We found that the tail vein injection of IRN (4 mg/kg) significantly increased the survival rate of PQ-intoxicated rats. IRN administration alleviated PQ-induced renal injury and renal dysfunction in rats, as evidenced by decreased apoptosis in renal cortex and reduced serum creatinine, serum BUN , and urine NGAL levels. Furthermore, IRN treatment improved the PQ-triggered oxidative stress in renal cortex by increasing the levels of anti-oxidant indicators (SOD activity, GSH/GSSG ratio, levels of Nrf-2, NQO-1, and HO-1 in renal cortex) and decreasing the levels of oxidative stress indexes (ROS and MDA levels in renal cortex). Interestingly, toll-interacting protein (Tollip), a negative regulator of interleukin 1 receptor associated kinase 1 (IRAK1) phosphorylation, was demonstrated to be increased by IRN injection in the renal cortex of PQ-intoxicated rats. In vitro experiments revealed that IRN protected renal tubular epithelial cells against PQ toxicity through suppressing oxidative stress and mitochondrial damage, and these protective effects were reversed by Tollip shRNA . Collectively, the present study demonstrated that IRN ameliorated PQ-induced AKI by attenuating oxidative stress and mitochondrial damage through upregulating Tollip, which provides new insights into the pathogenesis and treatment of PQ poisoning.
研究领域:
药理学
·
毒理学
·
肾脏生理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2021
·
IF 3.517
Keju Zhang,Yuhong Zhang,Yulin Li,Zoya Iqbal,Li Yu,Jiyan Liu,Haiping Wang,Peixin He
The synthesis of drug delivery systems based on hollow mesoporous silica nanoparticles (MSNs) is still a major challenge. In this work, the hollow hybrid MSNs were successfully prepared by cetyltrimethylammonium bromide-directed sol-gel process and one-step hydrothermal treatment process. The hollow hybrid MSNs had hybrid ethane-bridged frameworks with the uniform particle size (250 nm) and mesoporous pore diameter (3.7 nm). The polyacrylic acid (PAA) encapsulated drug delivery system based on hollow hybrid MSNs was prepared by using silanization, surface modification, doxorubicin hydrochloride (DOX) loading, and PAA coating. Drug encapsulation and release behavior at different temperatures and pH were studied by using DOX as a model guest molecule. The results displayed that the modified hollow ethane-bridged MSNs possessed good biocompatibility and excellent thermal/pH-dual-sensitive drug release property. This novel thermal/pH-sensitive drug delivery system based on hollow ethane-bridged MSNs has the advantages of feasible synthesis, no cytotoxicity, and good drug loading capacity, which may have potential applications in the anticancer therapy.
研究领域:
材料科学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Wentao Wang,Qicheng Zhang,Ming Zhang,Xintong Lv,Zihan Li,Mohsen Mohammadniaei,Ninglin Zhou,Yi Sun
Wound bacterial infections and tumor recurrence are the main reasons for the poor prognosis after primary tumor resection. Here, we fabricated a novel therapeutic nanocomposite using chitosan (CS) hydrogel combined with black phosphate nanosheets (BPNSs) and in situ grown copper nanoparticles (CuNPs). The obtained hydrogel ( [email protected] @CuNPs), possessing a remarkable temperature-sensitive spongy-like state, offered 24.98 % blood clotting index. The released [email protected] could produce reactive oxygen species (ROS) to kill infected invasive bacteria (98.1 %) and inhibit local residual tumor cell regeneration (11.3 %). Moreover, by coupling the photothermal properties of BPNSs , the [email protected] showed 19.6 % penetration rate to cross the blood tumor barrier (BTB) for treating brain tumors. The hydrogel platform was further combined with aPD-L1-based immunotherapy to employ its synergetic therapeutic effect in the prevention of tumors. The in vivo studies showed that biodegradable hydrogel could hold a great potential as a novel strategy for improving postoperative therapy and multi-tumor treatments.
研究领域:
生物医学工程
·
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2020
·
IF 3.968
Yan Lin,Moussa Harouna Koumba,Suxuan Qu,Dongxu Wang,Lianjie Lin
Ulcerative colitis-associated colorectal cancer (UC-CRC) is the most serious complication of ulcerative colitis (UC). Nuclear factor of activated T cells 3 (NFATc3) is participated in inflammation and cancer. In this study, we investigated the effects of NFATc3 on experimental UC-CRC in vivo and in vitro , and explored the underlying mechanisms. Administration of azoxymethane (AOM) and dextran sulfate sodium (DSS) induced UC-CRC model in C57BL/6 mice. Body weight was monitored weekly. Colon tissues were harvested at week 14. We examined changes in the histopathology, inflammatory cytokines, carcinogenesis factors, and epithelial-mesenchymal transition (EMT) markers in colon tissues. We found that NFATc3 expression was significantly up-regulated in AOM/DSS treated mice compared with control. Mice lacking NFATc3 showed decreased tumor number and size, decreased mucosal damage, and increased survival rate. Moreover, down-regulation of NFATc3 could inhibit the proliferation and EMT of UC-CRC, decrease the levels of pro-inflammatory cytokines, reduce the colonic infiltration by neutrophils and macrophages, and suppress the activation of P38 and JNK signal pathway in mice . In In vitro experiments, silencing NFATc3 suppressed the proliferation and EMT of CRC cells, and reduced the activation of P38 and JNK. In addition, miR-370-3p could bind to NFATc3. Down-regulation of miR-370-3p promoted proliferation and EMT of CRC cells, while silencing NFATc3 could reverse these effects. In conclusion, NFATc3 was involved in the pathogenesis of experimental UC-CRC and NFATc3 knockdown ameliorated experimental UC-CRC progression via the inhibition of inflammatory responses and EMT. NFATc3 mediated the inhibitory effects of miR-370-3p on CRC cells proliferation and EMT. Targeting NFATc3 may be effective in treating UC-CRC.
研究领域:
癌症生物学
·
免疫学
·
分子生物学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 475
·期 1
·1-13
·
IF 2.795
Lin Lin,Xin Bing,Jiang Tao,Wang Xin-lu,Yang Hua,Shi Tie-mei
Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Yinyin Liu,Zehao Li,Shuiyang Zou,Chunbo Lu,Yao Xiao,Hu Bai,Xiaoli Zhang,Haibo Mu,Xiuyun Zhang,Jinyou Duan
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital infection. Here, we showed that hyaluronic acid modified organic metal framework material ZIF-8 could be a Trojan horse of vancomycin (Van) for effective treatment of MRSA infections. The Van-loaded nanoparticles were readily up-taken by macrophages via a CD44-mediated process and collapsed in the acidic condition of endosome/lysosome, as a consequence, it could eradicate MRSA with high efficiency in macrophages. This drug delivery system with negligible toxicity could resolve MRSA infections in a well-established mouse pneumonia model.
研究领域:
药学
·
纳米技术
·
传染病学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Meng Du,Yuhao Chen,Jiawei Tu,Chun Liufu,Jinsui Yu,Zhen Yuan,Xiaojing Gong,ZhiYi Chen
Purpose: Gene therapy is an important therapeutic strategy for cancer. Nanoparticles are used for noninvasive gene delivery, which has great potential in tumor therapy. However, it is a challenge to construct a targeted gene delivery vector with high gene delivery efficiency, good biocompatibility, and multiple functions. Method: Herein, we designed magnetic mesoporous silica nanoparticle loading microbubbles (M-MSN@MBs) for ultrasound-mediated imaging and gene transfection. The plasmid DNA (pDNA) was encapsulated into the pores of M-MSNs. Also, the pDNA-carrying M-MSNs were loaded in the lipid microbubbles. Results: The gene vector presented good biocompatibility, DNA binding stability, ultrasound imaging performance, and magnetic responsiveness. The polyethyleneimine (PEI)-modified M-MSNs effectively protected the loaded pDNA from enzyme degradation. The cytotoxicity of M-MSNs was significantly reduced via encapsulating in lipid microbubbles. Upon the magnetic field, M-MSN@MBs were attracted to the tumor area. Then, ultrasound-targeted microbubble destruction (UTMD) not only released loaded M-MSNs but also facilitated M-MSNs delivery to tumor tissue by opening blood–tumor barrier and increasing the cytomembrane permeability, and ultimately improved the pDNA delivery efficiency. Conclusion: Our findings suggested that the developed ultrasound-responsive gene delivery system was a promising platform for gene therapy, which could noninvasively enhance tumor gene transfection.
研究领域:
肿瘤学
·
纳米医学
·
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）