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BIOMATERIALS · 2017 · IF 8.402

Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy

Qin Jiang,Zimiao Luo,Yongzhi Men,Peng Yang,Haibao Peng,Ranran Guo,Ye Tian,Zhiqing Pang,Wuli Yang

Photothermal therapy (PTT) has represented a promising noninvasive approach for cancer treatment in recent years. However, there still remain challenges in developing non-toxic and biodegradable biomaterials with high photothermal efficiency in vivo . Herein, we explored natural melanin nanoparticles extracted from living cuttlefish as effective photothermal agents and developed red blood cell (RBC) membrane-camouflaged melanin ( [email protected] ) nanoparticles as a platform for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles demonstrated strong absorption at NIR region , higher photothermal conversion efficiency (∼40%) than synthesized melanin-like polydopamine nanoparticles (∼29%), as well as favorable biocompatibility and biodegradability . It was shown that RBC membrane coating on melanin nanoparticles retained their excellent photothermal property, enhanced their blood retention and effectively improved their accumulation at tumor sites. With the guidance of their inherited photoacoustic imaging capability, optimal accumulation of [email protected] at tumors was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm laser , the developed [email protected] nanoparticles exhibited significantly higher PTT efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice. Given that both melanin nanoparticles and RBC membrane are native biomaterials, the developed [email protected] platform could have great potential in clinics for anticancer PTT.

研究领域: 生物医学工程 · 癌症研究 · 纳米技术 · 诊疗学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2017 · IF 3.671

Magnetic field-driven drug release from modified iron oxide-integrated polysaccharide hydrogel

Xinyu Hu,Yongmei Wang,Liangliang Zhang,Man Xu,Jianfa Zhang,Wei Dong

Salecan is a novel water-soluble extracellular β-glucan and suitable for the hydrogel preparation due to its excellent physicochemical and biological properties. The present article describes the fabrication and characterization of a pH/magnetic field-driven hydrogel based on salecan-g-poly(vinylacetic acid-co-2-hydroxyethyl acrylate) [poly(VA-co-HEA)] copolymer and Fe 3 O 4 @Agarose nanoparticles for drug release testing. Vibrating sample magnetometer characterization verified that integration of Fe 3 O 4 @Agarose nanoparticles in the copolymer provided the sensitivity to magnetic fields. The doxorubicin hydrochloride (DOX) release test showed a pH/magnetic field-triggered and sustained release property, and the release could be accelerated under mildly acidic conditions or the presence of an external magnetic field. Meanwhile, the increase in salecan content could also enhance the release rate. Cytotoxicity assays revealed that the released DOX maintained relatively high killing efficacy of A549 cells. In sum, these salecan-g-poly(VA-co-HEA)/Fe 3 O 4 @Agarose hydrogels were well-suited for magnetically targeted drug delivery systems.

研究领域: 药学 · 材料科学 · 纳米技术 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF INORGANIC BIOCHEMISTRY · 2015 · IF 3.444

The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)]2 +

Lan-mei Chen,Fa Peng,Guo-dong Li,Xin-ming Jie,Kang-rong Cai,Chun Cai,Yu Zhong,Hua Zeng,Wu Li,Zhen Zhang,Jin-can Chen

A new ruthenium methylimidazole complex [Ru(MeIm) 4 ( p -cpip)] 2   + ( Ru1 , p -cpip   =   2-(4-chlorophenyl)-1   H-imidazo[4,5-f][1,10]phenanthroline, MeIm   =   1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry , Comet assay , inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin . Further studies showed that Ru1 caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements.

研究领域: 肿瘤学 · 药理学 · 细胞生物学 · 化学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Ratiometric Fluorescence Imaging of Intracellular MicroRNA with NIR-Assisted Signal Amplification by a Ru-SiO2@Polydopamine Nanoplatform

Xunxun Deng,Xiaobo Liu,Shuo Wu,Shiyu Zang,Xiaotong Lin,Yanqiu Zhao,Chunying Duan

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM’s green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis.

研究领域: 生物医学工程 · 分子生物学 · 纳米技术 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2023 · IF 9.7

Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy

Rangrang Fan,Caili Chen,Junshan Hu,Min Mu,Di Chuan,Zhouyun Chen,Gang Guo,Jianguo Xu

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/ [email protected] NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/ [email protected] NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. Statement of significance To realize efficient tumor ablation under mild low-temperature (42–45 ℃) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/ [email protected] NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 分子生物学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 25 ·5856-5869 · IF 7

A calcium hydroxide/oleic acid/phospholipid nanoparticle induced cancer cell apoptosis by the combination of intracellular calcium overload and lactic acidosis elimination

Fei Zhou,Yang Yang,Yuying Liu,Haotian Deng,Jianhua Rong,Jianhao Zhao

Intracellular calcium ions (Ca2+) influence the proliferation–apoptosis balance, and lactic acidosis is an innate feature of a malignant tumor. In this study, a calcium hydroxide/oleic acid/phospholipid nanoparticle [CUR–Ca(OH)2-OA/PL NP] with lipase/pH dual responsive delivery of Ca2+ and curcumin (CUR) was developed for inducing cancer cell apoptosis by a combination of intracellular calcium overload and lactic acidosis elimination. The nanoparticle showed a core–shell structure with some good performance, including an adequate nano-size, negative charge, good blood circulation stability, and non-hemolysis. MDA-MB-231 breast cancer cells exhibited a higher lipase activity than A549 human lung adenocarcinoma cells and L929 mouse fibroblasts by fluorescence analysis. CUR–Ca(OH)2-OA/PL NPs were highly internalized by MDA-MB-231 cells, intracellularly released CUR and Ca2+, triggered the activation of caspase 3 and caspase 9, and caused apoptosis by intracellular calcium overload via a mitochondrial-mediated pathway. Lactic acid of 20 mM inhibited the apoptosis of MDA-MB-231 cells depending on the glucose insufficiency level, but this inhibition could be eliminated by CUR–Ca(OH)2-OA/PL NPs, leading to nearly complete apoptosis. Herein, CUR–Ca(OH)2-OA/PL NPs are a potential killer of cancer cells with high lipase activity by a combination of intracellular calcium overload and lactic acidosis elimination.

研究领域: 纳米技术 · 癌症生物学 · 药学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Pharmaceutics · 2020 ·Vol. 12 ·期 7 ·680 · IF 4.421

Oleic Acid Copolymer as A Novel Upconversion Nanomaterial to Make Doxorubicin-Loaded Nanomicelles with Dual Responsiveness to pH and NIR

Jin Zhang,Xiaoyue Tang,Chuanqing Huang,Zeyu Liu,Yong Ye

Oleic acid (OA) as main component of plant oil is an important solvent but seldom used in the nanocarrier of anticancer drugs because of strong hydrophobicity and little drug release. In order to develop a new type of OA nanomaterial with dual responses to pH and near infrared light (NIR) to achieve the intelligent delivery of anticancer drugs. The novel OA copolymer (mPEG-PEI-(NBS, OA)) was synthesized by grafting OA ando-nitrobenzyl succinate (NBS) onto mPEGylated polyethyleneimine (mPEG-PEI) by amidation reaction. It was further conjugated with NaYF4:Yb3+/Er3+nanoparticles, and encapsulated doxorubicin (DOX) through self-assembly to make upconversion nanomicelles with dual response to pH and NIR. Drug release behavior of DOX, physicochemical characteristics of the nanomicelles were evaluated, along with its cytotoxic profile, as well as the degree of cellular uptake in A549 cells. The encapsulation efficiency and drug loading capacity of DOX in the nanomicelles were 73.84% ± 0.58% and 4.62% ± 0.28%, respectively, and the encapsulated DOX was quickly released in an acidic environment exposed to irradiation at 980 nm. The blank nanomicelles exhibited low cytotoxicity and excellent biocompatibility by MTT assay against A549 cells. The DOX-loaded nanomicelles showed remarkable cytotoxicity to A549 cells under NIR, and promoted the cellular uptake of DOX into the cytoplasm and nucleus of cancer cells. OA copolymer can effectively deliver DOX to cancer cells and achieve tumor targeting through a dual response to pH and NIR.

研究领域: 纳米技术 · 药学 · 癌症研究 · 材料科学
✓ 已验证 DOI 高影响因子
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Chinese Herbal Medicines · 2022 · IF 0

An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities

Huan Zhang,Jun Kang,Wu-yan Guo,Fu-jie Wang,Meng-jiao Guo,Shan-shan Feng,Wu-ai Zhou,Jin-nan Li,Ayesha T. Tahir,Shao-shan Wang,Xin-jun Du,Hui Zhao,Wei-hua Wang,Hong Zhu,Bo Zhang

Objective Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. Methods PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. Results Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. Conclusion Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

研究领域: 药理学 · 毒理学 · 呼吸医学 · 中医药 · 分子生物学
✓ 已验证 DOI PubMed
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Journal of Radiation Research and Applied Sciences · 2020 · IF 1.804

DNA photocleavage, topoisomerase I inhibition, and cytotoxicities of two ruthenium complexes containing asymmetry ligand

Xue-Wen Liu,Ning-Yi Liu,Yuan-Qing Deng,Shan Wang,Ting Liu,Yu-Cai Tang,Yuan-Dao Chen,Ji-Lin Lu

ABSTRACT In recent years, ruthenium (II) complexes have attracted attention due to high DNA topoisomerase I inhibitory activities and good anticancer activities. Herein, an asymmetric ligand 2-(5-(1, 10-phenanthroline))-1 H-4,5-diphenyl-imidazole (pdpi) and its ruthenium complexes were synthesized. DNA-binding mode of two complexes was determined as intercalation by using UV–vis spectra, emission spectra, viscosity, and molecular docking experiments. DNA photocleavage experimental results show that two ruthenium complexes effectively cleave plasmid DNA by producing singlet oxygen. Furthermore, they both displayed good topo I inhibition activities. The cytotoxic activities results show that complex 2 displays better antitumor activities against Eca-109 cells and A549 cells (IC 50 = 25.97 ± 3.33 μM and 28.83 ± 2.49 μM, respectively) compared to complex 1 .

研究领域: 化学 · 药理学 · 癌症研究
✓ 已验证 DOI 高影响因子
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 3 ·1-7 · IF 5.479

Molecular beacon immobilized on graphene oxide for enzyme-free signal amplification in electrochemiluminescent determination of microRNA

Wang Jiaxing,Zhang Linlin,Lu Liping,Kang Tianfang

An electrochemiluminescence (ECL) based biosensor is described for determination of microRNAs in the A549 cell line. Firstly, graphene oxide (GO) is dripped onto a glassy carbon electrode surface to form an interface to which one end of the capture probe (with a stem-loop structure) can be anchored through π-interaction via dangling unpaired bases. The other end of the capture probe is directed away from the GO surface to make it stand upright. Target microRNAs can open the hairpin structure to form a double-stranded DNA-RNA structure. Two auxiliary probes, generating a hybridization chain reaction, are used to elongate the DNA duplex. Finally, doxorubicin-modified cadmium telluride quantum dot nanoparticles (Dox-CdTe QD) are intercalated into the base pairs of the hybrid duplexes to act as signalling molecules. The ECL signal of the Dox-CdTe QD increases proportionally with the concentration of microRNAs, specifically for microRNA-21. The assay covers a wide linear range (1 fM to 0.1 nM), has a low detection limit for microRNA-21 (1 fM), and is selective, reproducible, and stable. An enzyme-free amplification electrochemiluminescent assay is described to quantitative detection of microRNA in the A549 cell line. Graphene oxide was used to immobilize capture probes obviating the special modification. Doxorubicin-modified cadmium telluride quantum dot nanoparticles are intercalated into the base pairs of the hybrid duplexes to act as signalling molecules.

CAS / MDL: 10102-20-2
研究领域: 生物化学 · 纳米技术 · 分析化学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Chemical Biology · 2024 · IF 3.5

High-Throughput Computer Screen Aids Discovery of Methotrexate as miR-20b Inhibitor to Suppress Nonsmall Cell Lung Cancer Progression

Xiaorui Shi,Chong Hu,Liangli Fan,Bin Guo,Jingyu Zhang,Chu Tang,Fu Wang

MicroRNAs (miRNAs) play a significant role in tumor progression, and regulating miRNA expression with small molecules may offer a new approach to cancer therapy. Among them, miRNA-20b has been found to be dysregulated in several cancers, including nonsmall cell lung cancer (NSCLC). Herein, an in silico high-throughput computer screen was conducted to identify small molecules that downregulate miR-20b using the three-dimensional structure of the Dicer binding site on pre-miR-20b. Among 1058 small molecule compounds, Methotrexate (MTX), was discovered to be a potential miR-20b-specific inhibitor, which has been found to suppress miR-20b by specifically blocking Dicer processing in p53 wild-type A549 NSCLC cells but not in H1299 cells with p53 depletion. MTX effectively inhibited the proliferation, survival, migration, and invasion of A549 cells in a dose-dependent manner. Furthermore, the treatment of MTX up-regulated the expression of miR-20b target genes PTEN, STAT3, and HIF1α. Notably, MTX also significantly inhibited tumor growth in a mouse xenograft tumor model of NSCLC, with no observed tissue toxicity. Our findings indicate that MTX may have a novel role as an established drug in p53 wild-type NSCLC tumor therapy by down-regulating miR-20b expression. These findings are expected to provide preclinical evidence for miR-20b-targeting NSCLC therapeutic strategies.

研究领域: 肿瘤学 · 分子生物学 · 药理学 · 癌症治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2019 · IF 2.983

Novel chiral metal organic frameworks functionalized composites for facile preparation of optically pure propranolol hydrochlorides

Xue Ma,Wenrui Du,Yan Li,Chenfeng Hua,Ajuan Yu,Wuduo Zhao,Shusheng Zhang,Fuwei Xie

Two novel sorbents based on polydopamine (PDA)-coated magnetic graphite oxide-metal organic frameworks nanoparticles [Cu( L -mal)(bpy)]·H 2 O (MGO-CuLBH) and [Cu( D -mal)(bpy)]·H 2 O (MGO-CuDBH) possessing of both magnetic property and excellent enantioselective ability were prepared and characterized. Solutions of racemic propranolol hydrochloride ( Rac -PRO) were chosen to investigate the enantioselective performance of MGO-CuLBH and MGO-CuDBH by dispersive magnetic nanoparticle solid phase extraction (d-MNSPE). The results showed that the nanocomposites have excellent enantioselectivity to PROs with enantiomeric excess ( ee ) values reaching up to 98%. The entire process with PROs by the d-MNSPE method was fast, convenient and the collected composites could be easily recycled. Multi-stage operations using MGO-CuLBH and MGO-CuDBH were scaled up to obtain milligram quantities of R -propranolol hydrochloride ( R -PRO) and S -propranolol hydrochloride ( S -PRO). Furthermore, on the basis of the successful preparations, the differences in the cytotoxicity of Rac -PRO, R -PRO and S -PRO on A549 cells in vitro were all evaluated.

研究领域: 材料科学 · 药物化学 · 分析化学 · 生物技术
✓ 已验证 DOI PubMed 高影响因子
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