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ACS Applied Nano Materials · 2024 · IF 5.3

Light-Activated Silver Ion Release from Ag2Te Nanoparticles for Treating Drug-Resistant Bacterial Keratitis

Jingke Yao,Xunjie Shang,Jiayi Wei,Liting Guo,Feifan Sheng,Nannan Shao,Limin Chen,Zhe Zhang,Yunlong Zhou,Wei Chen

Biofilm and multidrug-resistant bacteria limit therapy effects on bacteria keratitis. Hence, we developed an all-in-one strategy based on a photothermal trigger to combat multidrug-resistant bacteria and eradicate biofilm. In the nanoplatforms, BSA-Ag2Te nanoparticles (NPs) fabricated by a one-step synthesis approach were utilized as photothermal agents to generate low temperature (40–48 °C) and then modified with RGD (Arg-Gly-Asp) to increase the drug concentration and retention in the cornea. The heat generated from photothermal therapy can accelerate the Ag+ release. In addition, laser-triggered release of Ag+ can significantly increase the ROS content in the bacteria. This synergistic approach could effectively eradicate multidrug-resistant bacteria and biofilm by photothermal therapy (PPT) and the combination of Ag+ and ROS. Based on the synergistic treatment of PTT, Ag+, and ROS, BSA-Ag2Te@RGD NPs exhibited outstanding antibacterial effects on a mice MRSA-infected keratitis model. BSA-Ag2Te@RGD NPs will be promising candidates for applications of low-temperature PTT in bacterial keratitis treatments.

CAS / MDL: 16940-66-2 13494-80-9
研究领域: 纳米技术 · 生物医学工程 · 眼科学 · 药学 · 细菌学
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JOURNAL OF DRUG TARGETING · 2021 · IF 5.121

Tumour microenvironment-responsive nanoplatform based on biodegradable liposome-coated hollow MnO2 for synergistically enhanced chemotherapy and photodynamic therapy

Xiangtian Deng,Qingcheng Song,Yiran Zhang,Weijian Liu,Hongzhi Hu,Yingze Zhang

Background Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system.Purpose This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies.Methods In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting.Results After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1’s downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学
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Acta Biomaterialia · 2023 · IF 9.7

Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds

Wenhui Qian,Guangming Gong,Hua Su,Yang Zhao,Wenjuan Fu,Yuting Wang,Wenwen Ji,Xuetong Sun,Bei Zhang,Lijuan Ma,Jianting Li,Xiangying Zhang,Su Li,Enze Sheng,Yin Lu,Dong Zhu

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml −1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. Statement of significance 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds

CAS / MDL: 9005-38-3
研究领域: 生物医学工程 · 毒理学 · 生物传感器 · 分子生物学 · 药学
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis

Caijie Yuan,Yaxin Ye,Enling Hu,Ruiqi Xie,Bitao Lu,Kun Yu,Weiwei Ding,Wenyi Wang,Guangqian Lan,Fei Lu

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO 3 /cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

CAS / MDL: 17465-86-0
研究领域: 药学 · 纳米技术 · 药物递送系统 · 血栓 · 生物医学工程
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Journal of Materials Chemistry B · 2015 ·Vol. 4 ·期 5 ·910-919 · IF 4.726

Hybrid polymeric nano-capsules loaded with gold nanoclusters and indocyanine green for dual-modal imaging and photothermal therapy

Wei Gu,Qi Zhang,Ting Zhang,Yingying Li,Jian Xiang,Rui Peng,Jian Liu

Currently there is a great need to design nano-carriers which enable multi-modal imaging of tumors and administration of therapeutics with high efficacy simultaneously. Herein we report a facile and robust approach to fabricate multifunctional nano-capsules based on double emulsions. The hybrid nano-capsules were loaded with BSA capped gold nanoclusters (AuNCs) and indocyanine green (ICG) for dual-modal imaging and effective photothermal therapy. RGD peptides were conjugated onto the surface of the hybrid nano-capsules to target cells overexpressing integrin ανβ3. We demonstrated that the as-prepared nano-capsules can be used for both one-photon and two-photon fluorescence imaging of tumor cells, and subsequent photothermal ablation with high effectiveness. The background noise of tissue autofluorescence was dramatically suppressed in the two-photon imaging mode. Therefore, it assisted a great deal to acquire images with a high signal-to-noise ratio using the hybrid nano-capsules. Due to a unique combination of the one-photon/two-photon fluorescence imaging and highly-effective photothermal properties, the hybrid nano-capsules may find broad biomedical applications as attractive theranostic nanomaterials.

CAS / MDL: 3599-32-4
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 成像科学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Biodegradable Hollow Polydopamine@manganese Dioxide as an Oxygen Self-Supplied Nanoplatform for Boosting Chemo-photodynamic Cancer Therapy

Haiyang Wang,Wenbo Wang,Lu Liu,Meng Wang,Guowei Li,Hang Li,Bo Li,Siming Yu,Dong Ma,Wei Xue

Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatform─HPDA@MnO2@Ce6/DOX@PEG-RGD (HPMRCD)─by means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO2), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and H2O2-rich TME. The dual-responsive release of Mn2+ ions and oxygen (O2) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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ADVANCED MATERIALS · 2022 ·Vol. 34 ·期 37 ·2204585 · IF 32.086

Herpesvirus-Mimicking DNAzyme-Loaded Nanoparticles as a Mitochondrial DNA Stress Inducer to Activate Innate Immunity for Tumor Therapy

Xiu Zhao,Yiyang Wang,Wenxiao Jiang,Qiongwei Wang,Jun Li,Zhiyang Wen,Airong Li,Kaixiang Zhang,Zhenzhong Zhang,Jinjin Shi,Junjie Liu

Virus-based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses is highly desirable for effective tumor immunotherapy but remains challenging. Here, inspired by the robust innate immunity induced by herpesvirus, a herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) is engineered for tumor therapy by mimicking the structure and infection processes of herpesvirus. In this biomimetic system, DNAzyme-loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF-90) nanoparticles (ZM@TD) mimic the virus nucleocapsid containing the genome; the erythrocyte membrane mimics the viral envelope; and two functional peptides, RGD and HA2 peptides, resemble the surface glycoprotein spikes of herpesvirus. Vir-ZM@TD can both effectively evade rapid clearance in the blood circulation and closely mimic the serial infection processes of herpesvirus, including specific tumor targeting, membrane fusion-mediated endosomal escape, and TFAM (transcription factor A, mitochondrial) deficiency-triggered mitochondrial DNA stress, as well as the release of manganese ions (Mn 2+ ) from organelles into the cytosol, ultimately effectively priming cGAS-STING pathway-mediated innate immunity with 68% complete regression of primary tumors and extending by 32 days the median survival time of 4T1-tumor-bearing mice.

CAS / MDL: 6156-78-1 5970-45-6
研究领域: 生物医学工程 · 癌症免疫疗法 · 纳米技术 · 分子生物学 · 细胞生物学 · 免疫学
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Biomaterials Science · 2023 · IF 6.6

An Fe-organic framework/arginine–glycine–aspartate peptide-modified sensor for electrochemically detecting nitric oxide released from living cells

Tingting Zhao,Ting Shu,Jinrong Lang,Ziyu Cui,Ping Li,Shi Wang

Nitric oxide (NO) is a crucial cell-signaling molecule utilized in numerous physiological and pathological processes. Monitoring cellular levels of NO requires a sensor with sufficient sensitivity, transient recording capability, and biocompatibility. Owing to the large surface area and high catalytic activity of the metal–organic framework, Fe–BTC was used for the modification of screen-printed electrodes (SPEs). This study investigates the electrochemical sensing of NO on modified SPEs. Additionally, the introduction of a cell-adhesive molecule, arginine–glycine–aspartate peptide (RGD), considerably improved the cytocompatibility, resulting in superior cell attachment and growth on the SPE. The Fe–BTC/RGD-modified SPE (Fe–BTC/RGD/SPE) exhibited electrocatalytic NO oxidation at 0.8 V, demonstrating a linear response with a detection limit of 11.88 nM over a wide concentration range (0.17–47.37 μM) and a response time of approximately 0.9 s. Subsequently, the as-obtained Fe–BTC/RGD/SPE was successfully utilized for the real-time detection of NO released from human endothelial cells cultured on the electrode. Therefore, the study undertaken shows remarkable potential of Fe–BTC/RGD/SPE for practical applications in biological processes and clinical diagnostics.

研究领域: 生物医学工程 · 电化学 · 细胞生物学 · 分析化学 · 生物技术
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ACS Biomaterials Science & Engineering · 2022 · IF 5.395

Strategy of Stem Cell Transplantation for Bone Regeneration with Functionalized Biomaterials and Vascularized Tissues in Immunocompetent Mice

He Zhang,Xiaoming Fu,Siqi Zhang,Qian Li,Yang Chen,Hao Liu,Wen Zhou,Shicheng Wei

The use of human bone marrow mesenchymal stem cells (hBMSCs) to regenerate and repair bone tissue defects is a complex research field of bone tissue engineering; nevertheless, it is a hot topic. One of the biggest problems is the limited survival and osteogenic capacity of the transplanted cells within the host tissue. Even for hBMSCs with their low immunogenicity, the body will still cause a local immune-inflammatory response directed against the allogeneic cells and thereby reduce the activity of the transplanted cells. Even in the case of successful transplantation, the lack of vascularization at the transplantation site makes it difficult for the transplanted cells to exchange nutrients and metabolic wastes that ultimately affects bone regeneration. In this study, we covalently modified alginate with RGD and QK peptides that were injected subcutaneously into immunocompetent mice. Histological analysis, as well as ELISA techniques, proved that this method is able to provide bioactive stem cell transplant beds containing functionalized biomaterials and vascularized surrounding tissues. Inflammation-related factors, such as IL-2, IL-6, TNF-α, and IFN-γ, around the cell graft beds decreased with time and were lowest at the second week. Then, the hBMSCs were injected into the cell transplantation beds intended to form vascularized bonelike tissues that were evaluated by micro-computed tomography (Micro CT), histological, and immunohistochemical analyses. The results showed that the expression of osteogenesis-related proteins RUNX2, COL1A1, and OPN, as well as the expression of angiogenic factor vWF and cartilage-related protein COL2A1 were significantly upregulated in the hBMSC-derived osteogenic tissue. These results suggest that the stem cell transplantation strategy by constructing bioactive cell transplant beds is effective to enhance the bone regeneration capacity of hBMSCs and holds great potential in bone tissue engineering.

研究领域: 组织工程 · 干细胞生物学 · 生物材料科学 · 免疫学 · 再生医学
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Bioactive Materials · 2024 · IF 18

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis

Kun Liu,Lin Li,Yizhi Li,Yiting Luo,Zhaoyu Zhang,Wei Wen,Shan Ding,Yadong Huang,Mingxian Liu,Changren Zhou,Binghong Luo

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

CAS / MDL: 9012-76-4
研究领域: 生物材料 · 组织工程 · 生物力学 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Bioorthogonal surface-edited exosomes for targeted multimodal imaging and synergic chemophototherapy of oral cancer

Yuxiao Wu,Xiaofeng Shan,Yuanjie Zhang,Wen Shi,Xingxing Zhu,Mengfan Yu,Shang Xie,Lingfeng Guo,Zhiqian Chen,Chuanling Zhang,Demin Zhou,Zhigang Cai

The highly invasive and infiltrative nature of oral cancer blurs the boundary between tumor and normal tissue. The study aimed to develop a targeted nanodrug delivery system utilizing natural biomaterial functionalities to improve the accuracy of oral cancer diagnosis and treatment. In this study, we synthesized RGD-modified exosomes (RGD-EXO) as a targeted nanodrug delivery system to load a coordination compound of indocyanine green and cisplatin (ICG-DDP), collectively known as ID@RGD-EXO, aiming to achieve multimodal imaging and synergistic chemophototherapy for oral cancer. The fluorescence intensity of ID@RGD-EXO is significantly increased compared to ICG. ID@RGD-EXO demonstrated promising potential for noninvasive fluorescence, photoacoustic, and infrared thermal imaging, enabling the comprehensive visualization of oral cancer’s structural and molecular characteristics for precise diagnosis. Laser irradiation-mediated temperature assists in breaking the ICG-DDP coordination bond and destabilizing the exosome membrane, enabling faster site-specific release of DDP to mitigate systemic toxicity of chemotherapy. ICG-mediated phototherapy and low-dose DDP-mediated chemotherapy demonstrated a strong synergistic antitumor effect, significantly improving the therapeutic outcomes for oral cancer. Furthermore, we utilized ID@RGD-EXO to effectively trace metastatic sentinel lymph nodes (SLN), showcasing its strong aggregation, excellent optical properties, enhanced photothermal effect, outstanding biocompatibility, and minimal toxicity. An advanced, low-toxicity nanomedical drug delivery system has been engineered to transport FDA-approved photoreactive and chemical drugs for precise diagnosis, synergistic chemophototherapy, as well as for tracing and ablating metastatic lymph nodes in oral cancer. This groundbreaking research holds great promise for clinical implementation.

CAS / MDL: 67-68-5 14913-33-8
研究领域: 癌症生物学 · 纳米医学 · 药学 · 成像科学 · 生物技术
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2017 · IF 2.31

Hyaluronic acid and Arg-Gly-Asp peptide modified Graphene oxide with dual receptor-targeting function for cancer therapy

Yufeng Guo,Haixing Xu,Yiping Li,Fengzheng Wu,Yixuan Li,Yun Bao,Xiumei Yan,Zhijun Huang,Peihu Xu

Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.

研究领域: 纳米技术 · 药学 · 癌症研究 · 生物医学工程
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