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JOURNAL OF FLUORESCENCE · 2025 · IF 3.1

A Facile Ratiometric Fluorescent Biosensor Using Blue-emitting Carbon Dots and Acriflavine for Quantitative Detection of DNA

Fang Fang,Cao Hongyu,Lu Jialu,Chen Nannan,Zhang Lu,Chen Yang

Carbon dots (CDs)-based ratiometric fluorescence strategies have attracted considerable attention. In this study, we developed a facile ratiometric fluorescent biosensor for DNA detection by utilizing the blue-emitting carbon dots (BCDs) as the fluorophore and acriflavine (AF), a fluorescent biological stain reagent, as both the response and recognition molecules. When AF was added, the fluorescence of BCDs decreased effectively and accompanied by a hypsochromic shift from 448 to 425 nm, whereas the fluorescence of AF at about 500 nm appeared due to the synergistic effect of Förster resonance energy transfer (FRET) and the inner filter effect (IFE) between the BCDs and AF. In the presence of DNA, the intercalative binding of AF into the DNA helix resulted in the fluorescence quenching of AF and the fluorescence restoration of BCDs at the same time. Therefore, the quantitative detection of DNA can be carried out vis evaluating the fluorescence intensity ratio of F 425 /F 500 . Under optimized conditions, the developed fluorescence method had an excellent linear range from 0 to 90 µM and a low detection limit of 0.52 µM. In addition, satisfactory results were obtained for the analysis of DNA in synthetic and real samples, with spiked recoveries ranging from 90.1 to 101.3%, demonstrating the enormous potential of the developed sensing platform for bioanalysis and biodetection. Graphical

研究领域: 生物传感器 · 分析化学 · 纳米技术 · 生物分析 · 荧光光谱
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2019 · IF 2.606

A novel approach for tailored medicines: Direct writing of Janus fibers

Zhi-Cheng Yao,Jun-Chuan Wang,Baolin Wang,Zeeshan Ahmad,Jing-Song Li,Ming-Wei Chang

Recent explorations have shown potential drug delivery applications of random and aligned fibrous dosage forms (e.g. patches, dressings, films and inserts). In this study, novel controlled delivery dosage forms, comprising Janus fibers, are designed and fabricated using electrohydrodynamic (EHD) engineering. Model probe and active compound release is shown from dissimilar polymer systems (non-soluble and soluble in nature) which constitute towards Janus systems. Micron scaled aligned Janus fibers comprising polycaprolactone (PCL) and polyvinyl pyrrolidone (PVP) were engineered to host rhodamine B and acriflavine , respectively. The impact of various operating parameters (e.g. flow rate, collector speed, working distance and applied voltage) on resulting mean fiber diameter and shape were optimized. Tensile strain decreased from 116.5 ± 10.2% to 81.8 ± 9.5% upon the inclusion of the model compounds, while both PCL/PVP and PCL/PVP/dyes samples exhibited similar tensile strength (∼0.65 MPa). FTIR analyses demonstrates PCL/PVP blend behavior and successful incorporation of rhodamine B and acriflavine. Acriflavine release from PCL fibers spanned over a 4-day period, and release of rhodamine B from PVP fibers was just over 6 h. The results indicate the EHD direct-jetting technique enables the precise construction of drug loaded and aligned fibers in a single-step with minimal excipient usage for potential customized drug delivery.

CAS / MDL: 8048-52-0 81-88-9
研究领域: 药剂学 · 生物材料学
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Cells · 2021 ·Vol. 10 ·期 6 ·1359 · IF 6.6

Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity

Nashwa Amin,Shijia Chen,Qiannan Ren,Xiaoning Tan,Benson O. A. Botchway,Zhiying Hu,Fengpei Chen,Shan Ye,Xiaoxue Du,Zuobing Chen,Marong Fang

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.Keywords:endothelin-1;hypoxia-inducible factor-1;interleukin 10;astrocyte;dimethyloxalylglycine;acriflavine;proinflammatory cytokines

CAS / MDL: 117399-94-7(free)
研究领域: 神经科学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2017 · IF 6.319

Tumor acidity-activatable manganese phosphate nanoplatform for amplification of photodynamic cancer therapy and magnetic resonance imaging

Yongwei Hao,Cuixia Zheng,Lei Wang,Jinjie Zhang,Xiuxiu Niu,Qingling Song,Qianhua Feng,Hongjuan Zhao,Li Li,Hongling Zhang,Zhenzhong Zhang,Yun Zhang

Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra-sensitive pH-responsive degradability and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway . Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1α/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1α /VEGF pathway timely while enhancing the MRI effect. Statement of Significance In this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway.

CAS / MDL: 87199-17-5
研究领域: 癌症治疗 · 纳米技术 · 分子成像 · 生物医学工程
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Materials Today Nano · 2022 · IF 13.364

A novel, liposome-loaded, injectable hydrogel for enhanced treatment of choroidal neovascularization by sub-tenon's injection

J. Li,Q. Tian,H. Sun,Y. Zhang,X. Yang,P. Kaur,R. Wang,Y. Fang,H. Yan,X. Du,L. Ye,G. Zhai

As a common multifactor fundus lesion, choroidal neovascularization (CNV) has become the leading cause of severe vision loss in the elderly. The mainstay treatment is an invasive intravitreal injection of anti-VEGF drug, which leads to a short half-life, incomplete response, and severe ocular complications. In this work, we have developed a novel, liposome-loaded, injectable hydrogel (cSA@Lip-HAC) by a minimally invasive sub-tenon's injection for CNV treatment. First, the multitarget angiogenic inhibitor (sunitinib) and hypoxia-inducible factor inhibitor (acriflavine) were co-loaded in the liposome, which was then loaded in the injectable hydrogel. The in vitro results showed that the cSA@Lip-HAC group had a strong anti-angiogenesis effect. After sub-tenon's injection, the hydrogel endowed the drug-loaded liposome with a longer retention time in the target area. In the CNV model, cSA@Lip-HAC showed a significant anti-CNV effect, which was superior to that of intravitreal injection of a commercial product (Conbercept). Exploration of the molecular mechanism revealed that cSA@Lip-HAC did not only inhibit CNV through the AKT/mTOR/HIF-1α/VEGF signal pathways but also inhibit VEGF R1 and VEGF R2. In conclusion, this novel drug delivery system, combining the merits of the liposome and hydrogel, showed an enhanced anti-CNV effect, thus providing a new and minimally invasive alternative for the treatment of neovascular ocular diseases.

研究领域: 眼科学 · 药学 · 药物递送系统 · 分子生物学
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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

Ultrastable Iodinated Oil-Based Pickering Emulsion Enables Locoregional Sustained Codelivery of Hypoxia Inducible Factor-1 Inhibitor and Anticancer Drugs for Tumor Combination Chemotherapy

Zhihua Li,Xiaoya Liu,Jingyu Xiao,Hang Jiang,Le Ma,Yucheng Luo,Meijuan Wang,Yuwei Zhu,Hongliang Jiang,Hanyang Yao,To Ngai,Qiongyu Guo

Tumor hypoxia-associated drug resistance presents a major challenge for cancer chemotherapy. However, sustained delivery systems with a high loading capability of hypoxia-inducible factor-1 (HIF-1) inhibitors are still limited. Here, we developed an ultrastable iodinated oil-based Pickering emulsion (PE) to achieve locally sustained codelivery of a HIF-1 inhibitor of acriflavine and an anticancer drug of doxorubicin for tumor synergistic chemotherapy. The PE exhibited facile injectability for intratumoral administration, great radiopacity for in vivo examination, excellent physical stability (>1 mo), and long-term sustained release capability of both hydrophilic drugs (i.e., acriflavine and doxorubicin). We found that the codelivery of acriflavine and doxorubicin from the PE promoted the local accumulation and retention of both drugs using an acellular liver organ model and demonstrated significant inhibition of tumor growth in a 4T1 tumor-bearing mouse model, improving the chemotherapeutic efficacy through the synergistic effects of direct cytotoxicity with the functional suppression of HIF-1 pathways of tumor cells. Such an iodinated oil-based PE provides a great injectable sustained delivery platform of hydrophilic drugs for locoregional chemotherapy.

CAS / MDL: 1336-21-6
研究领域: 药学 · 癌症研究 · 生物医学工程 · 药物递送系统
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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
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Pharmaceutics · 2024 ·Vol. 16 ·期 5 ·619 · IF 4.9

Cell-Membrane-Coated Metal–Organic Framework Nanocarrier Combining Chemodynamic Therapy for the Inhibition of Hepatocellular Carcinoma Proliferation

Huaying Xie,Xuhua Xiao,Xiaoyuan Yi,Kunzhao Huang,Liyan Wang

Chemodynamic therapy (CDT) employs hydrogen peroxide (H2O2) within the tumor microenvironment (TME) to initiate the Fenton reaction and catalyze the generation of hydroxyl radicals (·OH) for targeted therapy. Metal ion-based nanomaterials have garnered significant attention as catalysts due to their potent anti-tumor effects. Hypoxia in the TME is often associated with cancer cell development and metastasis, with HIF-1α being a pivotal factor in hypoxia adaptation. In this study, an organic framework called MIL-101 (Fe) was designed and synthesized to facilitate H2O2-induced ·OH production while also serving as a carrier for the HIF-1α inhibitor Acriflavine (ACF). A biomimetic nanomedical drug delivery system named MIL-101/ACF@CCM was constructed by encapsulating liver cancer cell membranes onto the framework. This delivery system utilized the homologous targeting of tumor cell membranes to transport ACF, inhibiting HIF-1α expression, alleviating tumor hypoxia, and catalyzing ·OH production for effective tumor eradication. Both in vivo and in vitro experiments confirmed that combining ACF with chemotherapy achieved remarkable tumor inhibition by enhancing ROS production and suppressing HIF-1α expression.

CAS / MDL: 7646-79-9
研究领域: 肿瘤学 · 纳米医学 · 药理学
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Chiral Polymer-Organic Molecule Composite with Circularly Polarized Thermally Activated Delayed Fluorescence and Room-Temperature Phosphorescence by Bridging Effect of Hydrogen Bond

Ruilian Chen,Rui Feng,Zhenjie Huang,Dengchong Feng,YuBo Long,Jiawen Zhang,Yuzhao Yang,Zetong Ma,Zhongke Yuan,Shaolin Lu,Zujin Zhao,Xudong Chen

Circularly polarized luminescence is essential to chiral and photonic science, but achieving circularly polarized thermally activated delayed fluorescence (CP-TADF) and circularly polarized room-temperature phosphorescence (CP-RTP) simultaneously remains a great challenge. This is because it is difficult to satisfy simultaneously the stable triplet exciton, appropriate energy gap, and the regular chiral environment. Herein, a simple strategy is reported to construct a persistent photoluminescent system, which can achieve TADF and RTP simultaneously by suppressing the non-radiative transition decay of the triplet exciton through intermolecular hydrogen bonding between acridine flavin (AF) and rigid polymer network. The persistent photoluminescent composite exhibited ultra-long lifetimes and high quantum yields. Then, a rarely multi-circularly polarized photoluminescence system containing CP-TADF and CP-RTP is constructed by the co-assembly of cellulose nanocrystals, polyvinyl alcohol, and AF. By utilizing the cholesteric structure, photonic band gap of chiral photonic crystals, and the stabilization mechanism of triplet exciton by intermolecular hydrogen bonding between the light emitter and rigid polymer, chiral photoluminescent films exhibited rare optical properties simultaneously: multi-circularly polarized photoluminescence emission, high and tunable dissymmetric factor, significant quantum yield, and ultralong lifetimes, which are not reported before and broaden the perspective for multi-circularly polarized luminescence.

研究领域: 材料科学 · 光学 · 光子学 · 化学
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