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SENSORS AND ACTUATORS B-CHEMICAL · 2015 · IF 4.097

Dual-functional cubic cuprous oxide for non-enzymatic and oxygen-sensitive photoelectrochemical sensing of glucose

Hongbo Li,Jing Li,Daye Chen,Yanxia Qiu,Wei Wang

A novel non-enzymatic and oxygen-sensitive photoelectrochemical (PEC) sensor for glucose was first constructed based on dual-functional cubic cuprous oxide. Herein, cuprous oxide acts both as an excellent catalyst for the preoxidation of glucose and as a photocathode for the PEC non-enzymatic glucose sensing. The fabricated cuprous oxide was characterized by scanning electron microscopy, X-ray diffractometry, X-ray photoelectron spectrometry, and UV–vis spectrophotometry. Under the optimized conditions, the PEC sensing was linear in its response to the logarithm of concentration of glucose in the range of 0.0005 to 6   mmol   L −1 with a detection limit of 0.3   μmol   L −1 . The same concentration of other common species did not interfere with the detection of glucose, and the results of the PEC sensor corresponded well with those obtained by the commercially available enzymatic glucose sensor. This novel non-enzymatic and oxygen-sensitive PEC sensor exhibited good performance with its high sensitivity, good selectivity, wide linear range, low cost, and portable features. Also it provides an alternative way for improving non-enzymatic PEC sensor of glucose.

研究领域: 生物传感器 · 材料科学 · 分析化学
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BIOMACROMOLECULES · 2019 · IF 5.667

NIR-Triggered Multifunctional and Degradable Nanoplatform Based on an ROS-Sensitive Block Copolymer for Imaging-Guided Chemo-Phototherapy

Chao Wang,Baoxuan Huang,Guoliang Yang,Yingjie Ouyang,Jia Tian,Weian Zhang

Imaging-guided chemo-phototherapy based on multifunctional nanocarriers has emerged as a promising and high-efficient cancer treatment because of the inevitable limitations of single therapy. Herein, a near-infrared (NIR) light-activated degradable polymeric nanoplatform was fabricated for chemo-phototherapy. An NIR photosensitizer, IR780, and a chemotherapeutic drug, doxorubicin (DOX), were efficiently coloaded within a reactive oxygen species (ROS)-sensitive polymeric micelle based on an amphiphilic copolymer with degradable thioketal (TK) linkages. The obtained spherical nanoparticles (denoted as (IR780/DOX)@PTK) exhibited a notable photodynamic and photothermal effect upon NIR light exposure. Furthermore, due to the rapid cleavage of TK linkers induced by ROS generated from NIR-activated IR780, (IR780/DOX)@PTK also showed an NIR light-induced degradable feature, which can be used for light-triggered tumor-specific drug release and lead to ignorable systematic toxicity after biodegradation and drug delivery. Under the guidance of NIR fluorescence and photothermal dual modal imaging, (IR780/DOX)@PTK exhibited excellent tumor accumulation after intravenously injection into 4T1-tumor-bearing mice. As verified in both in vitro and in vivo study, (IR780/DOX)@PTK presented a significant tumor suppression effect by synergistic chemo-phototherapy.

研究领域: 生物医学工程 · 肿瘤治疗学
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2021 ·Vol. 32 ·期 8 ·3113-3122 · IF 3.665

Hypoxia-sensitive micelles based on amphiphilic chitosan derivatives for drug-controlled release

Zhiming Chen,Weiqiu Wen,Jianwei Guo

Natural chitosan (CS) is composed of a larger hydrophilic skeleton with great biocompatibility. A hypoxia sensitive amphiphilic conjugate (CS-NBCF) was synthesized by conjugating CS with nitrobenzyl chloroformate (NBCF). Subsequently, nano micelles with high stability (CMC = 0.0030 mg/ml) were formed by self-assembly of the polymers in deionized water. The hypoxia-responsive function was demonstrated by examining the size variations of polymeric micelles under the hypoxia conditions. Doxorubicin (DOX) was encapsulated into the micellar core, the drug loading and encapsulation efficiency of DOX were 15.0% and 52.6%, respectively. The in vitro release experiments showed that DOX could be released rapidly in hypoxic environment, and the release amount was up to 68% in 24 h. It was found from the cytotoxicity experiment that that the toxicity of the blank micelles was low, while DOX-loaded micelles exhibited a good anti-cancer effect under hypoxic conditions, and the cell inhibition rate of MCF-7 was high up to 63%. As a result, the demonstrated properties endowed as-developed polymeric micelles with promising application as drug delivery system in tumor treatment.

研究领域: 药剂学 · 肿瘤学
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RSC Advances · 2015 ·Vol. 5 ·期 40 ·31972-31983 · IF 3.84

Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Yanjuan Wu,Dongfang Zhou,Yanxin Qi,Zhigang Xie,Xuesi Chen,Xiabin Jing,Yubin Huang

Novel intracellular pH, glutathione (GSH) and reactive oxygen species (ROS)-responsive nanoparticles were obtained using mPEG2k-block-redox dual sensitive chain-block-mPEG2k (PRDSP) which was prepared by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click polymerization. The disulfide bond, peroxalate ester and triazole units were regularly and repeatedly arranged in the hydrophobic blocks. The disulfide bond was GSH-sensitive and the peroxalate ester structure could be disrupted by acid and hydrogen peroxide. In addition, the triazole units are capable of forming pH-responsive hydrogen bonds. Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM) were used to investigate the pH, GSH and ROS sensitivity of the PRDSP nanoparticles (NPs). The results indicated that the average diameter, size distribution and morphology greatly changed upon adding GSH/H2O2 or modulating the pH. As the preloaded model anticancer drug, doxorubicin (DOX) was quickly released from DOX-loaded PRDSP (PRDSP@DOX) NPs by addition of 10 mM glutathione (GSH), or 10 mM H2O2 or under acidic conditions rather than under physiological conditions. Confocal laser scanning microscopy (CLSM) and flow cytometric analyses revealed that PRDSP@DOX could effectively deliver DOX into the cytoplasm and nucleus of cells. Therefore, PRDSP NPs may be a promising redox heterogeneity-sensitive carrier for efficient and controlled anticancer drug release.

研究领域: 生物材料学 · 药剂学 · 肿瘤治疗
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RSC Advances · 2022 ·Vol. 12 ·期 18 ·11477-11483 · IF 4.036

Investigation on fluorescein derivatives with thermally activated delayed fluorescence and their applications in imaging

Zhaoye Lv,Jun Hou,Junjie Yao,Ye Yuan,Yulan Qian,Junyang Zhu,Hongjuan Zhao,Xiaoqing Xiong,Chengqi Jiao

Fluorescein derivatives with thermally activated delayed fluorescence (TADF) show much stronger competition ability and vaster prospects than traditional fluorescein dyes due to their prominent long lifetime. It will be of great significance to synthesize more fluorescein derivatives with TADF. In this work, compounds DCF-MPYA and FL with TADF properties were obtained by fine tuning the substituents' structure on the basis of fluorescein derivative DCF-MPYM. Their long-lived triplet excited states (21.78 μs, 32.0 μs) were proved by nanosecond time-resolved transient difference absorption spectra. The steady-state and time-resolved fluorescence spectra showed that DCF-MPYA and FL exhibited red fluorescence around 645 nm and 651 nm, respectively. The results of sensitivity to oxygen and heavy atoms further demonstrated that the time-resolved fluorescence spectra originate from the delayed fluorescence. The time correlated single-photon counting (TCSPC) data indicated that DCF-MPYA and FL showed long-lived lifetimes of 13.16 μs and 23.72 μs, respectively. The energy gap (ΔEST) between the singlet (S1) and triplet (T1) states of DCF-MPYA and FL was calculated to be 3.32 meV and 9.98 meV from the decay rate of DF as a function of temperature. The small energy gap is conducive to the occurrence of efficient TADF at room temperature. Meanwhile, Gaussian calculation was employed to observe the electron density of DCF-MPYA and FL in the ground and excited states. The calculation results indicate that the shapes and energy levels of the highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs), and LUMOs+1 for the monoanion and dianion forms are similar and thus DCF-MPYA and FL exhibit almost the same luminescence properties. Finally, DCF-MPYA and FL with low toxicity were used in confocal and time-resolved fluorescence imaging. Our construction strategy will be beneficial for developing more fluorescein derivatives with TADF in the future.

研究领域: 化学 · 生物学 · 医学成像
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Nanoscale · 2013 ·Vol. 5 ·期 24 ·12633-12644 · IF 6.233

Hypoxia-sensitive bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium[poly(n-butyl cyanoacrylate]/chitosan nanoparticles and their phosphorescence tumor imaging in vitro and in vivo

Yun Zeng,Shaojuan Zhang,Menghui Jia,Yang Liu,Jin Shang,Youmin Guo,Jianhua Xu,Daocheng Wu

A new hypoxia-sensitive coordination compound, bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium[poly(n-butyl cyanoacrylate)], hereafter denoted as (btp)2Ir(PBCA), is synthesized and characterized by 13C nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). (btp)2Ir(PBCA)/chitosan [(btp)2Ir(PBCA)/CS] nanoparticles (NPs) with a core–shell structure are prepared by a two-step fabrication process. The size distributions of these NPs are measured with a Malvern size analyzer, and their morphology is observed by transmission electron microscopy (TEM). The functional groups on the surface are confirmed by FTIR. Phosphorescence spectra are obtained and lifetimes are determined with a spectrophotofluorometer and a time-correlated single photon counting (TCSPC) apparatus, respectively. HeLa and CT26 cell lines are used to examine the cytotoxicity by the MTT assay, as well as to determine the imaging capability of the samples in air and nitrogen atmospheres, respectively. Tumor-bearing mouse models of colon adenocarcinoma are used for tumor imaging in vivo, and the imaging effect is evaluated with a Maestro 2 fluorescence imaging system. Compared with the hypoxia-associated probe bis(2-(2′-benzothienyl)pyridinato-N,C3′)iridium(acetylacetonate) (BTP), the phosphorescence lifetime of (btp)2Ir(PBCA)/CS NPs significantly decreases, but the hypoxia-sensitivity increases after preparation of NPs. Apart from the significantly lower cytotoxicity, (btp)2Ir(PBCA)/CS NPs also enhance the tumor imaging effect by more than 10 times, maintaining the phosphorescence signal in tumor tissue for over 24 h and significantly decreasing the phosphorescence signal in normal tissue in vivo compared with the BTP probe.

研究领域: 生物医学工程 · 肿瘤学 · 材料科学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Sequential Diagnosis and Treatment for Colon Cancer via Derived Iridium and Indocyanine Green Hybrid Nanomicelles

Liang Yu,Yan Peng,Linping Jiang,Liyan Qiu

Indocyanine green (ICG) has been widely explored for the theranostics of tumors. However, ICG mainly accumulates in the liver, spleen, or kidney in addition to in tumors, causing inaccurate diagnoses and impaired therapeutic effects under NIR irradiation. Herein, a hybrid nanomicelle was constructed by integrating hypoxia-sensitive iridium(III) and ICG for precise tumor localization and photothermal therapy in sequence. In this nanomicelle, the amphiphilic iridium(III) complex (BTPH)2Ir(SA-PEG) was synthesized through the coordination substitution of hydrophobic (BTPH)2IrCl2 and hydrophilic PEGlyated succinylacetone (SA-PEG). Meanwhile, PEGlyated ICG (ICG-PEG) as a derivative of the photosensitizer ICG was also synthesized. (BTPH)2Ir(SA-PEG) and ICG-PEG were coassembled by dialysis to form the hybrid nanomicelle M-Ir-ICG. Hypoxia-sensitive fluorescence, ROS generation, and the photothermal effect of M-Ir-ICG were investigated in vitro and in vivo. The experimental results indicated that M-Ir-ICG nanomicelles could locate at the tumor site first and then perform photothermal therapy with 83.90% TIR, demonstrating great potential for clinical applications.

研究领域: 癌症研究 · 纳米技术 · 药学 · 生物医学工程
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POLYMER INTERNATIONAL · 2020 ·Vol. 69 ·期 7 ·619-626 · IF 2.574

Acid-sensitive reactive oxygen species triggered dual-drug delivery systems for chemo-photodynamic therapy to overcome multidrug resistance

Liping Yin,Yanli Bao,Lin Liu,Jinze Wang,Li Chen

In clinical treatment, multidrug resistance (MDR) is one of the major obstacles resulting in the failure of chemotherapy. It is still a challenge to overcome MDR. Herein, we fabricated intelligent dextran-based dual-drug delivery systems histidine modified dextran conjugated doxorubicin/zinc porphyrin/paclitaxel (DHTD/Zn-TPP/PTX) via supramolecular metallo-coordination for synergistic chemo-photodynamic therapy to overcome cancer drug resistance. In this designed DHTD/Zn-TPP/PTX, one anticancer drug (doxorubicin, DOX) was conjugated on the dextran backbone through a reactive oxygen species sensitive linker and the other drug PTX was encapsulated into the acid responsive supramolecular micelles formed by the photosensitizer Zn-TPP and histidine grafted on dextran. DHTD/Zn-TPP/PTX with excellent stability could be effectively internalized by tumour cells. In the acidic tumour environment, the loaded PTX and Zn-TPP as photosensitizer could be released; moreover, when irradiated with light the conjugated DOX could be specifically released because the linker broke. As the obtained data indicate, DHTD/Zn-TPP/PTX exhibited not only an enhanced anticancer therapeutic effect but also significant growth inhibition for drug-resistant MCF-7/ADR cells to reverse MDR, having great potential for synergistic treatments of cancer to overcome MDR. © 2020 Society of Chemical Industry

研究领域: 肿瘤学 · 药物递送 · 生物材料
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery

Xianshuo Zhang,Peipei Wang,Xinsheng Wang,Yaoyu Xu,Taolin Cheng,Chengjie Zhang,Jiaying Ding,Yunfeng Shi,Wei Ma,Cui-Yun Yu,Hua Wei

Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility , biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β -cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly( ε -caprolactone)- b -poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL- b -PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL- b -PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% ( P1 ) and 20 wt% ( P2 ) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1 -based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1 -based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.

研究领域: 纳米医学 · 癌症研究 · 药物递送系统 · 材料科学
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AAPS PHARMSCITECH · 2022 ·Vol. 23 ·期 6 ·1-11 · IF 4.026

A Hypoxia-Sensitive Drug Delivery System Constructed by Nitroimidazole and its Application in the Treatment of Hepatocellular Carcinoma

Meng Tingting,Li Yinghong,Tian Ying,Ma Mingxing,Shi Kequan,Shang Xuwei,Yuan Hong,Hu Fuqiang

Hypoxia is an important pathological phenomenon, and it can induce many tumor microenvironment changes, such as accumulations of intracellular lactic acid, decrease of tumor microenvironment pH value, and regulate a series of physiological and pathological processes such as adhesion, metastasis, and immune escape. Hypoxic tumor cells act as a key target for treating tumor. In this research, we designed and prepared PEG-nitroimidazole grafts, PEG-NI, and FA-PEG-NI. We first explored their physical and chemical properties to serve as a drug carrier. Then, the hypoxia-sensitive properties such as particle size changes and drug release were investigated. Finally, the tumor targeting ability was studied in vitro and in vivo , and anti-tumor capacity was determined. Both grafts showed excellent property as a nanodrug carrier and showed favorable drug encapsulation ability of sorafenib with the help of the hydrophobic chain of 6-(BOC-amino) hexyl bromide. The micelles responded to the hypoxic tumor environment with chemical and spatial structure changes leading to sensitive and fast drug release. With the modification of folic acid, FA-PEG-NI gained tumor targeting ability in vivo . FA-PEG-NI graft proved a potential targeting drug delivery system in the treatment of hypoxic hepatocellular carcinoma. Graphical Abstract

CAS / MDL: 527-73-1 142356-33-0
研究领域: 药理学 · 肿瘤学 · 分子生物学 · 生物医学工程
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JOURNAL OF CONTROLLED RELEASE · 2020 · IF 7.727

Hypoxia-sensitive supramolecular nanogels for the cytosolic delivery of ribonuclease A as a breast cancer therapeutic

Xinghui Si,Sheng Ma,Yudi Xu,Dawei Zhang,Na Shen,Haiyang Yu,Yu Zhang,Wantong Song,Zhaohui Tang,Xuesi Chen

As the most common malignancy in women, breast cancer causes >40,000 deaths annually. Ribonuclease A (RNase), a new anti-cancer agent, has attracted intense interest due to its high efficacy and specificity. However, RNase suffers from instability, a short half-life in the circulation and poor membrane penetration. To overcome these challenges, we designed a supramolecular nanogel for the cytosolic delivery of RNase. The nanogels were fabricated using host–guest interactions between azobenzene (Azo) and β-cyclodextrin (βCD) conjugated to poly (L-glutamic acid)- graft -poly (ethylene glycol) methyl ether (PLG- g -mPEG). RNase could be loaded inside the nanogels in mild aqueous conditions. Following optimization, the RNase-loading content and efficiency of the nanogel were 23.5 wt% and 50.4%, respectively. In the presence of nitroreductase (NTR), the cross-linking point between Azo and βCD was destroyed due to the conformation transition of Azo, ensuring the hypoxia-sensitive release of cargo from the nanogels in tumors in which NTR is overexpressed. In vitro release profiles revealed that 75.0% of the RNase was released under hypoxic conditions in 72 h, whilst only 19.7% was released under normoxic conditions. Cytotoxicity assays showed that the RNase-loaded nanogels (nano-RNase) were more efficient in inhibiting the proliferation of 4T1 cells than free RNase. In vivo studies showed 68.7% tumor suppression rates (TSR %) in the nano-RNase treated group, whilst free RNase treatment led to a lack of tumor inhibition. To further enhance the hypoxia status of tumors, we combined nano-RNase with a nanoformulation of vascular disrupting agents PLG- g -mPEG/combretastatinA4 (nano-CA4) and obtained a TSR of 91.7%. The hypoxia-sensitive supramolecular nanogels provided a versatile platform for the delivery of RNase, highlighting its applicability for cancer therapy.

研究领域: 药学 · 癌症研究 · 纳米技术 · 药物递送系统
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MOLECULES · 2022 ·Vol. 27 ·期 20 ·6929 · IF 4.927

Functionalized Ultrasmall Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging of Tumor Hypoxia

Lei Yang,Mohammad Javad Afshari,Jianxian Ge,Dandan Kou,Lei Chen,Dandan Zhou,Cang Li,Shuwang Wu,Leshuai Zhang,Jianfeng Zeng,Jian Zhong,Roland H. Stauber,Mingyuan Gao

Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitiveT1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia viaT1-weighted MRI. These promising results may unlock the potential of Fe3O4nanoparticles asT1-weighted contrast agents for the development of clinical hypoxia probes.Keywords:tumor hypoxia;ultrasmall iron oxide nanoparticles;magnetic resonance imaging;metronidazole

研究领域: 医学影像 · 纳米技术 · 肿瘤学 · 生物医学工程
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