Materials Today Bio
·
2024
·
IF 8.7
Xuan Zhang,Xia Gao,Xiangzhou Yi,Hui Yu,Mingyang Shao,Yongcheng Li,Xuanri Shen
The pathogenesis of ulcerative colitis (UC) is closely related to severe inflammation, damaged colonic mucosal barrier, increased oxidative stress and intestinal ecological imbalance. However, due to the nonspecific distribution and poor bioavailability of drugs, UC treatment is still a serious challenge. Here, a mitochondria/colon dual targeted nanoparticles based on redox response was developed to effectively alleviate UC. Cannabidiol nanoparticles (CBD NPs) with a particle size of 143.2 ± 3.11 nm were prepared by self-assembly using polymers (TPP–IN–LA) obtained by modifying inulin with (5-carboxypentyl) triphenyl phosphonium bromide (TPP) and α-lipoic acid (α-LA). Excitingly, the constructed CBD NPs showed excellent mitochondrial targeting, with a Pearson correlation coefficient of 0.76 at 12 h. The results of animal imaging in vivo showed that CBD NPs could be effectively accumulated in colon tissue. Not only that, CBD showed significant glutathione stimulated release in the presence of 10 mM glutathione at pH 7.4. The results of in vivo animal experiments showed that CBD NPs significantly ameliorated DSS-induced colonic inflammation by modulating the TLR4-NF-κB signaling pathway. Moreover, CBD NPs significantly improved the histological damage of colon in UC mice, increased the expression level of tight junction protein ZO-1, and effectively restored the intestinal mucosal barrier function and intestinal mucosal permeability. More importantly, CBD NPs significantly improved the species composition, abundance and amount of short chain fatty acids of intestinal flora in UC mice, thus effectively maintaining the balance of intestinal flora. The dual-targeted and glutathione-responsive nanoparticles prepared in this study provide a promising idea for achieving targeted delivery of CBD for effective treatment of UC.
研究领域:
药学
·
纳米技术
·
炎症性肠病
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药物递送系统
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结直肠疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Mengyun Peng,Hongyan Dong,Meiyu Shao,Xiaoqing Zhang,Jiamei Sun,Chuan Ding,Xin Han,Qiao Yang,Xianan Sang,Gang Cao
Hepatocellular carcinoma (HCC) is an immunosuppressive tumor associated with high mortality. Photothermal and photodynamic therapies have been applied to induce immunogenic cell death (ICD) in HCC, successfully eliciting immune responses but facing limitations in penetration depth in clinical trials . Here, intrinsic mitochondrial hyperthermia was used to trigger thermosensitive drug release. The mitochondria were further self-heated through 2,4-dinitrophenol uncoupling, dramatically promoting free radical initiation and inducing tumor ICD. The synthesized mitochondrial-targeting TPP-HA-TDV nanoparticles specifically generated free radicals in the mitochondria without external stimulation, and obviously enhanced the release of ICD markers, subsequently evoking immune responses. The results showed that mitochondrial hyperthermia could be an endogenous target for thermosensitive drug release. Furthermore, self-heating mitochondria-induced free radical blast could be an efficient therapeutic for deep-seated tumor therapy.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Zaigang Zhou,Wenjuan Luo,Chunjuan Zheng,Haoxiang Wang,Rui Hu,Hui Deng,Jianliang Shen
Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF- β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro , which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF- β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CONTROL
·
2019
·
IF 4.248
Wenjing Yan,Wenbin Chen,Umair Muhammad,Jianhao Zhang,Hong Zhuang,Guanghong Zhou
The aim of this work was to prepare a novel antioxidant film by incorporating α-tocopherol-chitosan nanoparticles (TOC-CSNPs) with chitosan/montmorillonite film (namely, TOC-CSNPs/CS/MMT), and investigate the antioxidant activity of TOC-CSNPs/CS/MMT film on sliced dry-cured ham in a period of 120 days at 4 °C. Positively charged TOC-CSNPs with the average sizes of 214 nm were prepared using TPP-initiated ionic gelation mechanism. The amount of TOC-CSNPs was optimized based on the changes of water vapor permeability (WVP), water solubility and swelling ratio of the film. The TOC-CSNPs/CS/MMT film showed 46.5% radical scavenging activity after 16 days of storage, which was 23 times and 27 times higher than that of CS/MMT and CS film, respectively. The antioxidant activity of TOC-CSNPs/CS/MMT film was evaluated by measuring the peroxide value (POV) and thiobarbituric acid reactive substances (TBARS) values of sliced dry-cured ham coated with the TOC-CSNPs/CS/MMT film-forming solutions. The results indicated that compared with the CS (0.42 g/100 g for POV, 0.65 mg/kg for TBARs) and CS/MMT (0.38 mg/kg for POV, 0.59 mg/kg for TBARs) films, the biceps femoris muscle of the sliced ham coated with TOC-CSNPs/CS/MMT film showed much lower values of POV (0.15 g/100 g) and TBARs (0.15 mg/kg) during 120 days of storage. These results provide a theoretical basis for developing efficient and long-term antioxidant approach, which is crucial for improving and enhancing the quality of food products.
研究领域:
食品科学
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材料科学
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化学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 45
·1903850
·
IF 15.621
Yaru Cheng,Fan Yang,Kai Zhang,Yiyi Zhang,Yu Cao,Conghui Liu,Huiting Lu,Haifeng Dong,Xueji Zhang
Here, in terms of the highly reactive oxidative hydroxyl radical (•OH) generation ability of isoniazid (INH) catalyzed by Mn 2+ ion and the photothermal effect of WSSe nanoflakes, a WSSe/MnO 2 -INH nanocomposite for synergistic anticancer treatment is developed. Advanced INH-induced •OH formation ability is systemically demonstrated in the presence of manganese and relevant non-Fenton-type mechanism, and good photothermal conversion efficiency of the WSSe/MnO 2 nanocomposite. After modifying with mitochondria-targeted triphenylphosphonium bromide (TPP) moieties and camouflaging with cancer cells membrane (WSSe/MnO 2 -INH-TPP@CM), it confers a sequential cell-to-mitochondria targeting ability. In vivo X-ray computed tomography and magnetic resonance tumor imaging capability of the nanocomposite are also revealed. The mitochondria-targeted oxidative damage and photothermal therapy by WSSe/MnO 2 -INH-TPP@CM results in excellent anticancer treatment efficacy both in vitro and in vivo. This is the first exploration of the possibility of non-Fenton-type •OH formation for anticancer treatment, which opens new opportunities for ROS-based and combined cancer treatment strategies.
研究领域:
纳米技术
·
癌症研究
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药学
·
生物医学工程
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材料科学
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产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2021
·
IF 3.963
Chao Xu,Hongzhou Chen,Qinyan Wu,Yuqi Wu,Paul Daly,Jian Chen,Hongfu Yang,Lihui Wei,Yiqing Zhuang
Fusarium head blight( FHB )caused by Fusarium graminearum species complex (FGSC) is one of the most important diseases around the world. Deoxynivalenol (DON) is a type of mycotoxin produced by FGSC when infecting cereal crops . It is a serious threat to the health of both humans and livestock. Trehalose-6-phosphate phosphatase ( TPP ), a conserved metabolic enzyme found in many plants and pathogens, catalyzes the formation of trehalose. N-(phenylthio) phthalimide (NPP) has been reported to inhibit the normal growth of nematodes by inhibiting the activity of TPP , but this inhibitor of nematodes has not previously been tested against F. graminearum . In this study, we found that TPP in F. graminearum (Fg TPP ) had similar secondary structures and conserved cysteine (Cys356) to nematodes by means of bioinformatics. At the same time, the sensitivity of F. graminearum strains to NPP was determined. NPP exhibited a better inhibitory effect on conidia germination than mycelial growth . In addition, the effects of NPP on DON biosynthesis and trehalose biosynthesis pathway in PH-1 were also determined. We found that NPP decreased DON production, trehalose content, glucose content and TPP enzyme activity but increased trehalose-6-phosphate content and trehalose-6-phosphate synthase ( TPS ) enzyme activity. Moreover, the expression of TR I 1 , TR I 4 , TR I 5 , TR I 6 , and TPP genes were downregulated, on the contrary, the TPS gene was upregulated. Finally, in order to further determine the control ability of NPP on DON production in the field, we conducted a series of field experiments, and found that NPP could effectively reduce the DON content in wheat grain and had a general control effect on FHB. In conclusion, the research in this study will provide important theoretical basis for controlling FHB caused by F. graminearum and reducing DON production in the field.
研究领域:
植物病理学
·
真菌学
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农学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 27
·4318-4323
·
IF 0
Jinfeng Xing,Jinhao Liu,Tingbin Zhang,Ling Zhang,Meiling Zheng,Xuanming Duan
Hydrogels with a precise 3D configuration (3D hydrogels) are required for a number of biomedical applications such as tissue engineering and drug delivery. Two-photon polymerization (TPP) is an advanced method to fabricate 3D hydrogels. However, TPP of 3D hydrogels has been challenged by the lack of TPP initiators with high efficiency in aqueous medium. In this study, a water soluble TPP initiator (WI) with high fabrication efficiency was prepared by combining hydrophobic 2,7-bis(2-(4-pentaneoxy-phenyl)-vinyl)anthraquinone (N) with a C2v symmetrical structure and 2-hydroxypropyl-β-cyclodextrins through host–guest chemical interaction. Both one and two-photon optical properties of WI have been investigated. In aqueous medium, WI showed a two-photon absorption cross-section of around 200 GM at the wavelength of 780 nm which was much higher compared with those of commercial initiators. The threshold energy of TPP for the resin with WI as a photoinitiator (the molar ratio of N in resin is 0.03%) was 8.6 mW. 3D hydrogels with a woodpile microstructure were further fabricated by using an average power of 9.7 mW and a scanning speed of 30 μm s−1.
研究领域:
材料科学
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生物医学工程
·
高分子化学
·
组织工程
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DOI
PubMed
Food & Function
·
2021
·Vol. 12
·期 17
·7718-7727
·
IF 5.396
Yannan Chen,Shanshan Tie,Xuedi Zhang,Lijuan Zhang,Mingqian Tan
Novel mitochondria targeting nanocarriers were prepared using triphenylphosphonium bromide (TPP)-modified whey protein isolate (WPI)–dextran (DX) conjugates by self-assembly method for astaxanthin mitochondria targeting delivery. The nanocarriers of astaxanthin-loaded WPI–DX and astaxanthin-loaded TPP–WPI–DX were 135.26 and 193.64 nm, respectively, which exhibited a spherical structure and good dispersibility. The mitochondria targeting nanocarriers had good stability in the stimulated blood fluid. In vitro experiments indicated that the TPP-modified nanocarriers could effectively realize lysosomes escape, and specifically accumulate in the cell mitochondria. Simultaneously, the astaxanthin-loaded nanocarriers could significantly reduce reactive oxygen species generation produced from hydrogen peroxide, protect the normal levels of the mitochondrial membrane potential, and dramatically promote the vitality of leukemia cells in mouse macrophage (RAW 264.7) cells. The present study highlights the promising application of mitochondria targeting nanocarriers for enhanced delivery of astaxanthin.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Qiqi Yin,Yanli Yao,Handan Zhang,Jie Zhang,Jiaming Gao,Lin Weng,Tao Liu,Shuyang Sun,Xin Chen
The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. We introduced a cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment. Utilizing iron oxide nanoparticles and mesoporous silica, we developed the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA). Triphenylphosphine (TPP) modification facilitated mitochondrial targeting, while tumor cell membrane (TCM) coating provided homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM nanoparticles demonstrated efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggered δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria underwent Fenton chemistry for CDT. The synergistic interaction of PDT and CDT mechanisms increased cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic and damage mechanisms, ultimately leading to enhanced tumor cell death. PDT/CDT-induced apoptosis generated δ-ALA-containing apoptotic bodies, enhancing anti-tumor efficacy in deep tumor cells. The advantageous anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing systemic side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
肿瘤学
·
治疗学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Mochou Gao,Xuehong Zhao,Wei Wang,Xueyan Zou,Chunpeng Song
Chain-like chitosan-sodium tripolyphosphate (CS-TPP) nanocomposite was prepared by an aqueous solution route. Then fluorescently active 6-carboxyl luciferin (6-FAM) was modified onto CS-TPP surface to afford CS-TPP-6-FAM nanocomposite (CS-TPP-6-FAM) with fluorescent activity. Onto the surface of CS-TPP-6-FAM was grafted bioactive carboxymethyl β -cyclodextrin (CβCD) to obtain CS/TPP/FAM/CβCD that can separate maltose binding protein tagged (MBP-tagged) fusion proteins from E. coli lysate. Findings demonstrate that CS-TPP-6-FAM-CβCD has an average diameter of 22 nm and a chain length of 70 nm. Its adsorption kinetic data can be described by Langmuir isotherm equation and the pseudo 2nd kinetic model , corresponding to high protein binding capacity for MBP-tagged PYL3. Furthermore, CS-TPP-6-FAM-CβCD dispersed in Hoagland nutrient solution can be adsorbed by tobacco through vascular bundle channels. Therefore, CS-TPP-6-FAM-CβCD could have promising applications in separating MBP-tagged fusion proteins from E. coli lysate and in monitoring the growth of plants as the fluorescent tracer.
研究领域:
纳米技术
·
生物技术
·
蛋白质工程
·
植物科学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2023
·
IF 15.1
Qing Zheng,Hanghang Liu,Hao Zhang,Yaobao Han,Jiaxin Yuan,Tingting Wang,Yifan Gao,Zhen Li
Mitochondrial dysfunction of neurons is the core pathogenesis of incurable Parkinson's disease (PD). It is crucial to ameliorate the mitochondrial dysfunction of neurons for boosting the therapy of PD. Herein, the remarkable promotion of mitochondrial biogenesis to ameliorate mitochondrial dysfunction of neurons and improve the treatment of PD by using mitochondria-targeted biomimetic nanoparticles, which are Cu 2- x Se-based nanoparticles functionalized with curcumin and wrapped with DSPE-PEG 2000 -TPP-modified macrophage membrane (denoted as CSCCT NPs), is reported. These nanoparticles can efficiently target mitochondria of damaged neurons in an inflammatory environment, and mediate the signaling pathway of NAD + /SIRT1/PGC-1 α /PPAR γ /NRF1/TFAM to alleviate 1-methyl-4-phenylpyridinium (MPP + )-induced neuronal toxicity. They can reduce the mitochondrial reactive oxygen species, restore mitochondrial membrane potential (MMP), protect the integrity of mitochondrial respiratory chain, and ameliorate mitochondrial dysfunction via promoting mitochondrial biogenesis, which synergistically improve the motor disorders and anxiety behavior of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. This study demonstrates that targeting mitochondrial biogenesis to ameliorate mitochondrial dysfunction has a great potential in the treatment of PD and mitochondria-related diseases.
研究领域:
神经科学
·
纳米技术
·
药理学
·
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）