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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

A “defend–attack and capture flag” strategy for cascade management of hepatic ischemia reperfusion injury

Wenze Zhang,Zhuoxia Shen,Chaoran Li,Yumeng Yang,Tiange Zhang,Bo-Yang Yu,Xianchuang Zheng,Jiangwei Tian

Hepatic ischemia reperfusion injury (HIRI) following transplantation or resection can lead to irreversible liver dysfunction and even failure, yet current therapeutic interventions are limited. Herein, we introduce a “defend–attack and capture flag” nanotheranostic strategy for the cascade management of HIRI. Firstly, the NIR-II photothermal pretreatment with the developed nanosystem provides preprotection for the liver, acting as “defend”. Subsequently, the pharmacotherapy furnishes direct cure for HIRI via the delivery and controlled release of wedelolactone from the nanosystem, serving as “attack”. Meanwhile, the photoacoustic (PA) imaging ability of the nanosystem enables the real-time monitoring of the inflammatory hypoxia, which is the “flag” to be captured in HIRI treatment. The photothermal preprotection can activate heat shock factor 1 (HSF-1), while the pharmaceutical therapy directly attacks NF-κB, both of which eventually inhibits NLRP3 inflammasome, thus reducing the activity of proinflammatory cytokine IL-1β, ending up with the alleviation of necrosis and apoptosis in HIRI. Such treatment effect can be reported by the real-time PA imaging. By the organic combination of the above three-step mechanism, significantly enhanced therapeutic efficacy was achieved in the animal model of HIRI, providing an effective solution for overcoming the challenge of HIRI.

研究领域: 纳米技术 · 药学 · 医学影像 · 移植医学 · 炎症生物学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Ultrathin CuFe2S3 nanosheets derived from CuFe-layered double hydroxide as an efficient nanoagent for synergistic chemodynamic and NIR-II photothermal therapy

Sa Wang,Tingting Hu,Guanyun Wang,Zhengdi Wang,Dan Yan,Ruizheng Liang,Chaoliang Tan

Ultrathin two-dimensional (2D) nanosheets (NSs) have been widely explored as nanoagents for multimodal cancer therapies, such as photothermal therapy (PTT) combined with chemodynamic therapy (CDT). However, it is still a challenge to prepare 2D NSs with good performance in both CDT and NIR-II PTT. Here, we report the preparation of ultrathin 2D CuFe 2 S 3 NSs as an efficient nanoagent for synergistic CDT and NIR-II PTT to ablate cancer cells/tumors. Ultrathin 2D CuFe 2 S 3 NSs are first prepared by sulfurization of ultrathin CuFe-LDH NSs via a simple hydrothermal treatment. After modification with polyethylene glycol (PEG), the PEG-modified CuFe 2 S 3 NSs (CuFe 2 S 3 -PEG) show broadband NIR-II absorption and excellent photothermal conversion efficiency (~55.86%) at 1064 nm. Moreover, the overproduced glutathione in the tumor microenvironment can react with CuFe 2 S 3 -PEG NSs to release Fe 2+ and Cu + , thus activating Fenton reaction to efficiently produce hydroxyl radicals (·OH). Importantly, the photothermal effect of CuFe 2 S 3 -PEG could further synergistically improve the Fenton reaction by increasing the local temperature. In vitro and in vivo results reveal that the CuFe 2 S 3 -PEG has remarkable synergistic CDT/PTT antitumor activity. This study has proven that the metal chalcogenide NSs of CuFe 2 S 3 -PEG can be used as an efficient nanoagent for multimodal cancer therapies, which could also be promising in other applications like biosensors, drug delivery and antibacterial.

研究领域: 癌症治疗 · 材料科学 · 纳米技术 · 生物医学工程
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Advanced Science · 2021 ·Vol. 8 ·期 20 ·2100894 · IF 16.806

3D Printed Wesselsite Nanosheets Functionalized Scaffold Facilitates NIR-II Photothermal Therapy and Vascularized Bone Regeneration

Chen Yang,Hongshi Ma,Zhiyong Wang,Muhammad Rizwan Younis,Chunyang Liu,Chengtie Wu,Yongxiang Luo,Peng Huang

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor-initiated bone defects. Such scaffolds are usually composed of a near-infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long-term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR-I) with intrinsic poor tissue penetration depth. Also, most of these agents are non-bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR-II photothermal conversion agent (Wesselsite [SrCuSi 4 O 10 ] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as-designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR-II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor-induced bone defects.

研究领域: 生物材料 · 生物医学工程 · 光热治疗 · 骨组织工程
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 41 ·9492-9501 · IF 5.344

A tumor-targeted theranostic nanomedicine with strong absorption in the NIR-II biowindow for image-guided multi-gradient therapy

Qi Chen,Ziliang Zheng,Xiaojing He,Shuo Rong,Yufei Qin,Xiaoyang Peng,Ruiping Zhang

Developing new strategies to enhance drug accumulation in the tumor and therapeutic efficacy is of great importance in the field of tumor therapy. Herein, a peanut-like multifunctional nanomedicine (CuS-PGH NMs) made of CuS nanoparticles encapsulated in poly(L-lysine)(PLL)/glucose oxidase (GOx)-hyaluronic acid (HA) shells has been constructed via layer-by-layer (LbL) assembly, and shows good biocompatibility and effective multi-gradient therapy. Because of the enhanced permeability and retention (EPR) effect, the CuS-PGH NMs could significantly enhance the cellular uptake by tumors overexpressing CD44 receptors, which respond to hyaluronidase (HAase)-triggered surface charge conversion. Once internalized by the tumor, GOx was the first to be exposed and could effectively deplete endogenous glucose for starvation therapy, and the excess H2O2 was then converted into highly toxic hydroxyl radicals (˙OH) via a Cu+-mediated Fenton-like reaction for chemodynamic therapy (CDT). Meanwhile, the as-obtained Cu+ ions accompanied the regenerated less-active Cu2+ ions. Interestingly, the high content of H2O2 could, in turn, accelerate Cu2+/Cu+ conversion to promote the Cu+–H2O2 reaction for enhanced chemodynamic therapy (CDT), thereby achieving efficient tumor growth suppression via synergistic starvation/CDT therapy. Subsequently, owing to the strong NIR-II absorption capability of CuS-PGH NMs, effective photothermal tumor ablation of the weakened tumor cells could be realized with the precise guidance of NIR-II PAI. This multi-gradient therapeutic strategy has been demonstrated to have excellent antitumor activity with minimal nonspecific damages, and offers a new avenue to precise tumor therapy.

研究领域: 纳米医药 · 肿瘤治疗 · 生物医学工程 · 药学
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JOURNAL OF NANOBIOTECHNOLOGY · 2022 ·Vol. 20 ·期 1 ·1-17 · IF 9.429

Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging

Lin Yuejun,Zhou Hui-chao,Chen Ningbo,Ren Yaguang,Gao Rongkang,Li Qiaojia,Deng Yiwen,Han Xuejiao,Zhang Xiaoran,Xiang Andy Peng,Guo Bing,Liu Chengbo,Ren Jie

Background Therapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far. Results Penetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSC Cxcr3 ). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSC Cxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSC Cxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis. Conclusions TAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy. Graphical Abstract

CAS / MDL: 8001-25-0
研究领域: 干细胞生物学 · 成像科学 · 分子生物学 · 治疗学
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 36 ·8323-8336 · IF 5.344

Defect-engineered transition metal hydroxide nanosheets realizing tumor-microenvironment-responsive multimodal-imaging-guided NIR-II photothermal therapy

Li Yang,Xiaojiao Zhu,Tianren Xu,Fusen Han,Gang Liu,Yingcui Bu,Jie Zhang,Feng Zhang,Hongping Zhou,Yi Xie

Exploiting two-dimensional nanomaterials as photo-based theranostic agents is promising for the highly efficient ablation of deep-tissue-buried tumors. However, they are limited by their poor absorption in the second near-infrared-light (NIR-II) bio-window (1000–1300 nm) and intrinsic nonbiodegradability. Herein, defect-rich sulfur-doped Ni(OH)2 (S-Ni(OH)2) nanosheets decorated with bovine serum albumin (BSA) as a novel theranostic agent is developed, which can accomplish multimodal-imaging-guided photothermal ablation of mouse cancers in the NIR-II bio-window. Sulfur doping extends the absorption spectra of Ni(OH)2 nanosheets from the visible to NIR-II bio-window, affording highly efficient photothermal conversion (58.20% for 1064 nm), entailing it to become an excellent contrast agent for photoacoustic imaging. Further, because of their intrinsic paramagnetic property, they can be applied for magnetic resonance imaging. Owing to the abundant defective sites in S-Ni(OH)2 nanosheets, they exhibit response to the tumor microenvironment, resulting in effective biodegradation and excretion from the body. In vivo toxicity experiments indicated that S-Ni(OH)2-BSA NSs delivered no appreciable toxicity and good biocompatibility. This work provides an avenue for the rational design of effective theranostics agents.

CAS / MDL: 100-97-0 7791-20-0
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学 · 医学成像
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