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Journal of Materials Chemistry B · 2023 · IF 7

Ultrasound-propelled nanomotors for efficient cancer cell ferroptosis

Ting Chen,Jie Yang,He Zhao,Dajian Li,Xiaoyong Luo,Zhiyu Fan,Biye Ren,Yuepeng Cai,Renfeng Dong

Ferroptosis is a non-apoptotic form of cell death that is dependent on the accumulation of intracellular iron that causes elevation of toxic lipid peroxides. Therefore, it is crucial to improve the levels of intracellular iron and reactive oxygen species (ROS) in a short time. Here, we first propose ultrasound (US)-propelled Janus nanomotors (Au–FeOx/PEI/ICG, AFPI NMs) to accelerate cellular internalization and induce cancer cell ferroptosis. This nanomotor consists of a gold–iron oxide rod-like Janus nanomotor (Au–FeOx, AF NMs) and a photoactive indocyanine green (ICG) dye on the surface. It not only exhibits accelerating cellular internalization (∼4-fold) caused by its attractive US-driven propulsion but also shows good intracellular motion behavior. In addition, this Janus nanomotor shows excellent intracellular ROS generation performance due to the synergistic effect of the “Fenton or Fenton-like reaction” and the “photochemical reaction”. As a result, the killing efficiency of actively moving nanomotors on cancer cells is 88% higher than that of stationary nanomotors. Unlike previous passive strategies, this work is a significant step toward accelerating cellular internalization and inducing cancer-cell ferroptosis in an active way. These novel US-propelled Janus nanomotors with strong propulsion, efficient cellular internalization and excellent ROS generation are suitable as a novel cell biology research tool.

研究领域: 生物医学工程 · 纳米技术 · 癌症研究 · 细胞生物学
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MICROCHIMICA ACTA · 2020 ·Vol. 187 ·期 11 ·1-9 · IF 6.232

Environmental and intercellular Pb2+ ions determination based on encapsulated DNAzyme in nanoscale metal-organic frameworks

Wu Weihao,Fan Yaofang,Tan Bing,Zhao Huimin

With the merits of low cost, simple synthesis procedure, and high affinity for metal ions, deoxyribozyme (DNAzyme) have played important roles in metal ions detection. However, the intracellular applications of DNAzyme are limited because of enzymatic degradation and inefficient cellular uptake. To address these problems, GR-5 as model DNAzyme was encapsulated into zeolitic imidazolate frameworks-8 (ZIF-8) nanoparticles by biomimetic mineralization. The positively charged ZIF-8 with high DNAzyme loading capacity retained their ability to enter cells. Compared with free DNAzyme, the biomimetic mineralization synthesis method has greatly improved the stability of pristine DNAzyme. The as-synthesized DNAzyme@ZIF-8 composite exhibited good stability resisting DNase I, and was used as a sensitive fluorescent nanoprobe for Pb 2+ determination and successfully achieved selective and sensitive determination for Pb 2+ at λ ex / λ em  = 494/522 nm in real samples. The linear range for the determination of Pb 2+ is 50 to 500 nM. Moreover, the highly active DNAzyme delivered by ZIF-8 allows noninvasive imaging of Pb 2+ measurement in living cells. This strategy will extend the suitability of functional nucleic acids for in vitro and in vivo bioanalysis and bioimaging. Graphical abstract

CAS / MDL: 693-98-1
研究领域: 生物化学 · 分析化学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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RSC Advances · 2020 ·Vol. 10 ·期 25 ·14915-14927 · IF 3.119

Double-edged effects and mechanisms of Zn2+ microenvironments on osteogenic activity of BMSCs: osteogenic differentiation or apoptosis

Yiqiang Yu,Kai Liu,Zhuo Wen,Weicai Liu,Lei Zhang,Jiansheng Su

Zinc-incorporated biomaterials show promoting effects on osteogenesis; however, excessive zinc ions lead to cytotoxic reactions and also have other adverse effects. Therefore, the double-edged effects of Zn2+ microenvironments on osteogenesis may become critical issues for new material development. This study systematically investigated the bidirectional influences of diverse Zn2+ microenvironments on the cell adhesion, proliferation, osteogenic differentiation and apoptosis of rBMSCs. Furthermore, the mechanisms of zinc-induced osteogenic differentiation of rBMSCs and of cell apoptosis induced by high concentration of Zn2+ were both discussed in detail. The results indicated that the Zn2+ microenvironments of 2 μg mL−1 and 5 μg mL−1 effectively improved the initial adhesion and proliferation of rBMSCs, while that of 15 μg mL−1 had exactly the opposite effect. More importantly, the suitable Zn2+ microenvironments (2 μg mL−1 and 5 μg mL−1) moderately increased the intracellular Zn2+ concentration by regulating zinc transportation, and then activated the MAPK/ERK signaling pathway to induce the osteogenic differentiation of rBMSCs. In contrast, the high Zn2+ concentration (15 μg mL−1) not only inhibited the osteogenic differentiation of rBMSCs by damaging intracellular zinc homeostasis, but also induced rBMSC apoptosis by enhancing intracellular ROS generation. The current study clarified the double-edged effects of Zn2+ microenvironments on the osteogenic properties of rBMSCs and the related mechanisms, and may provide valuable guidance for optimizing the design of zinc-doped biomaterials and zinc-based alloys.

CAS / MDL: 7446-20-0
研究领域: 生物材料 · 细胞生物学 · 组织工程 · 生物医学工程
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS · 2019 ·Vol. 31 ·期 1 ·175-181 · IF 2.195

Highly sensitive fluorescent sensing for intracellular glutathione based on Ti3C2 quantum dots

Xu Xiumei,Zhang Haijiao,Diao Quan,Zhu Yongsheng,Yang Gang,Ma Benyuan

Intracellular glutathione (GSH) sensing was important for monitoring many diseases and health of cell. In this study, we prepared surface-functionalized Ti 3 C 2 quantum dots (QDs) by ultrasonic cutting and hydrothermal method. Bright excitation wavelength-dependent blue emission was observed in Ti 3 C 2 QDs which was attributed to surface defects and quantum confinement effects. Furthermore, we developed a novel fluorescence sensor that can detect GSH with high sensitivity, based on the fluorescence resonance energy transfer process from Ti 3 C 2 quantum dots to GSH, with a detection limit of 0.02 μM approximately. This novel Ti 3 C 2 QD can be used as a promising fluorescent sensor for practical applications.

研究领域: 生物化学 · 纳米医学 · 分析化学
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Fe3+ and intracellular pH determination based on orange fluorescence carbon dots co-doped with boron, nitrogen and sulfur

Shengmei Song,Junhui Hu,Minglu Li,Xiaojuan Gong,Chuan Dong,Shaomin Shuang

The fluorescent boron, nitrogen and sulfur co-doped carbon dots (BNSCDs) were prepared by simple hydrothermal reaction of 4-carboxyphenylboronic acid and 2,5-diaminobenzenesulfonic acid at 200 °C for 8 h. The fluorescence of the BNSCDs could be quenched by Fe 3+ based on the electron transfer between Fe 3+ and BNSCDs, so a label-free, good selectivity and high sensitivity method for Fe 3+ determination was established with linear range and LOD of 1.5–692 μmol/L and 87 nmol/L, respectively. And then the fluorescent probe was employed for detection of Fe 3+ in tap water, coal gangue, fly ash and food samples successfully. Moreover, the as-prepared BNSCDs could serve as a novel pH fluorescent probe in the range of pH 1.60–7.00, which could be attributed to the proton transfer of carboxyl groups on the surface of BNSCDs. More importantly, the pH fluorescent probe possesses fast, real-time and low toxicity, applying for intracellular pH fluorescence imaging in HIC, HIEC, LO2 and SMMC7721 cells. In view of its simplicity, timely response and outstanding compatibility, the as-fabricated BNSCDs show the potential applications in water quality and solid waste monitoring, food detection, real-time measuring of intracellular pH change in vitro.

研究领域: 分析化学 · 生物医学工程 · 环境科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

Porphyrin derived dual-emissive carbon quantum dots: Customizable synthesis and application for intracellular Cu2+ quantification

Yuqian Liu,Farzad Seidi,Chao Deng,Ruyi Li,Tingting Xu,Huining Xiao

Exploring sensory systems from metal ion receptors enables the continuous development of ion sensing technologies. Herein we report the synthesis of carbon quantum dots (CQDs) from 5,10,15,20-tetrakis(4-sulfophenyl)porphyrin (TSPP) and additional carbon source, and its application in Cu 2+ imaging and quantifying in living cells. The CQDs are synthesized via a hydrothermal method in a successive polymerization and carbonization process. Due to the surface traps introduced by TSPP residue, the CQDs are featured with dual-emissive property of green (505 nm) and red (682 nm) fluorescence. Moreover, the red-to-green fluorescence ratio is readily customizable by tuning the molar fraction of TSPP. Benefited from Cu 2+ complexation induced red fluorescence quenching, the CQDs can be served as the ratiometric fluorescent nanosensor for Cu 2+ detection with ultra-high sensitivity and excellent specificity. The nanosensor is demonstrated to linearly detect Cu 2+ in the range of 0−50 nM, with an extremely low limit of detection (LOD) of 37 pM. More importantly, interference from other biological compositions, especially Fe 3+ , is successfully excluded via the site-selective coordination and specific electron transfer path. Based on the excellent analytical performance of the nanosensor, quantifying Cu 2+ in living cells is realized according to the linear correlation between fluorescence ratio and intracellular Cu 2+ content, which is parallelly detected by inductively coupled plasma mass spectrometry (ICP-MS). To demonstrate its practicality, the nanosensor is challenged to measure Cu 2+ uptake kinetics for cell lines derived from different tissues.

研究领域: 生物传感 · 材料科学 · 分析化学
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 7 ·1482-1497 · IF 4.543

Disulfide modified self-assembly of lipopeptides with arginine-rich periphery achieve excellent gene transfection efficiency at relatively low nitrogen to phosphorus ratios

Xiaobing Chen,Jun Yang,Hong Liang,Qian Jiang,Bowen Ke,Yu Nie

Integrating the advantages of artificial vectors with bioinspired strategies has opened interesting perspectives in the design of gene delivery systems. Herein, disulfide modified, self-assembled lipopeptides with arginine-rich periphery are demonstrated as gene vectors (RLS). It is surprising that these carriers achieved excellent gene transfection efficacy (up to 380-fold higher than PEI) in different cell lines (HeLa and B16 cells) at relatively low N/P (∼10) ratios, compared to the analog lipopeptides without disulfide bonds (RL, N/P 40). As shown from the morphologies observed by transmission electronic microscopy and surface charge detection by dynamic light scattering, the existence of disulfide bonds may influence the configuration/conformation of the RLS assembly with decreased zeta potential (+27.2 mV), compared to that of the analogs, RL (+46.5 mV). Correspondingly, RLS/DNA complexes showed relatively lower zeta potentials than those of RL/DNA complexes at different N/P ratios. Under the transfection conditions, RLS/DNA complexes (N/P 10) showed even less cellular uptake than that of RL/DNA complexes (N/P 40), and no difference was detected in buffering effect and endosomal escape between RLS and RL complexes. Examination by gel electrophoresis and fluorescence resonance energy transfer (FRET) images in cell culture conditions confirmed that RLS lipoplexes could effectively liberate DNA. Thus, the higher gene transfection efficiency of disulfide modified vectors might be mainly attributed to the cleavage of disulfide bonds; the rapid release of DNA and the superiority of the design was closely related to the reductive conditions in the cells.

研究领域: 生物化学 · 分子生物学 · 药物递送
✓ 已验证 DOI PubMed 高影响因子
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RSC Advances · 2020 ·Vol. 10 ·期 56 ·33635-33641 · IF 3.119

Fluorescent probe based on N-doped carbon dots for the detection of intracellular pH and glutathione

Meihua Lin,Xin Ma,Shijun Lin,Xiaojin Zhang,Yu Dai,Fan Xia

Carbon dots (CDs) as fluorescent probes have been widely exploited to detect biomarkers, however, tedious surface modification of CDs is generally required to achieve a relatively good detection ability. Here, we synthesized N-doped carbon dots (N-CDs) from triethylenetetramine (TETA) and m-phenylenediamine (m-PD) using a one-step hydrothermal method. When the pH increases from 3 to 11, the fluorescence intensity of the N-CDs gradually decreases. Furthermore, it displays a linear response to the physiological pH range of 5–8. Au3+ is reduced by amino groups on the surface of N-CDs to generate gold nanoparticles (AuNPs), causing fluorescence quenching of the N-CDs. If glutathione (GSH) is then added, the fluorescence of the N-CDs is recovered. The fluorescence intensity of the N-CDs is linearly correlated with the GSH concentration in the range of 50–400 μM with a limit of detection (LOD) of 7.83 μM. The fluorescence probe was used to distinguish cancer cells from normal cells using pH and to evaluate intracellular GSH. This work expands the application of CDs in multicomponent detection and provides a facile fluorescent probe for the detection of intracellular pH and GSH.

研究领域: 生物化学 · 分析化学 · 医学检测
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2020 · IF 9.038

Size-dependent cellular internalization and effects of polystyrene microplastics in microalgae P. helgolandica var. tsingtaoensis and S. quadricauda

Yingxin Chen,Yun Ling,Xinyu Li,Jiani Hu,Chengjin Cao,Defu He

Microplastics (MPs) are persistent contaminants in aquatic environments. Microalgae, as the main phytoplankton and primary producers, usually co-exist with MPs. Despite previous studies that have proved the interaction of MPs and microalgae, it is largely unknown whether MPs can be uptake into cells of microalgae. In this study, both marine P. helgolandica var. tsingtaoensis and freshwater microalgae S. quadricauda were respectively exposed to 10 mg/L polystyrene microbeads with five diameter sizes: 1.0, 2.0, 3.0, 4.0, and 5.0 μm. Confocal laser scanning and 3D image analysis showed that mean 24.0 % or 11.3 % cells of P. helgolandica var. tsingtaoensis contained 1.0 μm or 2.0 μm MPs after 72 h exposure. While mean 43.3 % or 15.3 % of S. quadricauda individuals engulfed 1.0 μm or 2.0 μm MPs within cells. But, none of 3.0–5.0 μm MPs were observed within algal cells. These results demonstrate the size-dependent cellular internalization of MPs in microalgae. Exposure to 1.0–2.0 μm PS MPs caused a significant reduction in the density of microalgae and influenced photosynthesis, which suggests cellular internalization of MPs can influence algal fertility and growth. This discovery first confirms cellular internalization of MPs in phytoplankton, of significance for the fate and eco-toxicity of MPs in the aquatic ecosystem.

CAS / MDL: 9003-53-6
研究领域: 环境科学 · 生物学
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Polymer Chemistry · 2012 ·Vol. 4 ·期 4 ·1199-1207 · IF 5.321

pH and reduction dual-responsive nanogel cross-linked by quaternization reaction for enhanced cellular internalization and intracellular drug delivery

Mingqiang Li,Zhaohui Tang,Hai Sun,Jianxun Ding,Wantong Song,Xuesi Chen

A novel pH and reduction dual-responsive nanogel with improved cellular internalization was prepared through atom transfer radical polymerization and subsequent quaternization reaction. Doxorubicin (DOX), a model anticancer drug, was loaded into the nanogel via dispersion. The DOX-loaded nanogel presented a stable core-cross-linked structure under physiological conditions, but quickly released its payload in an acidic (pH 6.8) and reductive (10.0 mM glutathione) environment. Confocal fluorescence microscopy and fluorescence flow cytometry revealed that the DOX-loaded nanogel could deliver DOX into the cytoplasm and nucleus of cells, more efficiently than that of free DOX. The improved cellular internalization was more significant under acidic and reductive conditions, which was analogous to the pH and reductive conditions in endosomes and cytoplasm. In vitro cytotoxicity studies demonstrated that the pH and reduction responsive DOX-loaded nanogel could inhibit cellular proliferation more efficiently than free DOX. This dual-bioresponsive nanogel with quaternary ammonium salt group has appeared to be highly promising in the further development of intracellular drug transporters.

CAS / MDL: 3483-12-3 70-18-8
研究领域: 药剂学 · 肿瘤学 · 生物材料学
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Surface Self-Assembly of Dipeptides on Porous CaCO3 Particles Promoting Cell Internalization

Yuqi Ma,Anhe Wang,Jieling Li,Qi Li,Qingquan Han,Yafeng Jing,Xuefang Zheng,Hongyu Cao,Xuehai Yan,Shuo Bai

The self-assembling behavior of peptides and derivatives is crucial in the natural process to construct various architectures and achieve specific functions. However, the surface or interfacial self-assembly, in particular, on the surface of micro- or nanoparticles is even less systematically investigated. Here, uniform porous CaCO3 microparticles were prepared with different charged, hydrophobic and hydrophilic surfaces to assess the self-assembling behavior of dipeptides composed of various sequences. Experimental results indicate that dipeptides with a negative charge in an aqueous solution preferred to self-assemble on the hydrophobic and positively charged surface of CaCO3 particles, which can be ascribed to the electrostatic and hydrophobic interaction between dipeptides and CaCO3 particles. Meanwhile, the Log p (lipid–water partition coefficient) of dipeptides has a significant effect on the self-assembling behavior of dipeptides on the surface of porous CaCO3; dipeptides with high Log p preferred to self-assemble on the surface of CaCO3 particles, resulting in the improved cell internalization efficiency of particles with low cytotoxicity. After loading with a model drug (doxorubicin), the particles show obvious antitumor activity in animal experiments and can reduce Dox side effects effectively.

CAS / MDL: 62-31-7
研究领域: 生物材料学 · 细胞生物学 · 药理学
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TALANTA · 2016 · IF 4.035

An intramolecular charge transfer process based fluorescent probe for monitoring subtle pH fluctuation in living cells

Mingtai Sun,Libo Du,Huan Yu,Kui Zhang,Yang Liu,Suhua Wang

It is crucial to monitor intracellular pH values and their fluctuation since the organelles of cells have different pH distribution. Herein we construct a new small molecule fluorescent probe HBT-O for monitoring the subtle pH values within the scope of neutral to acid in living cells. The probe exhibited good water solubility, a marked turquoise to olivine emission color change in response to pH, and tremendous fluorescence hypochromatic shift of ∼50   nm (1718   cm −1 ) as well as the increased fluorescence intensity when the pH value changed from neutral to acid. Thus, the probe HBT-O can distinguish the subtle changes in the range of normal pH values from neutral to acid with significant fluorescence changes. These properties can be attributed to the intramolecular charge transfer (ICT) process of the probe upon protonation in buffer solutions at varied pH values. Moreover, the probe was reversible and nearly non-toxic for living cells. Then the probe was successfully used to detect pH fluctuation in living cells by exhibiting different fluorescence colors and intensity. These findings demonstrate that the probe will find useful applications in biology and biomedical research.

研究领域: 生物化学 · 细胞生物学 · 医学研究
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