RSC Advances
·
2017
·Vol. 7
·期 79
·49931-49936
·
IF 3.108
Mengke Yuan,Yanjia Guo,Jianjia Wei,Jizhou Li,Tengfei Long,Zhongde Liu
Inspired by the knowledge that one usual method to impart chirality to metal nanoparticles is to passivate them with ligands possessing chirality, in this context, a pair of optically active blue-emitting carbon dots (CDs) were prepared using citric acid and D/L-penicillamine (D/L-Pen) as the carbon sources through a two-step pyrolytic route. The second line of our research related to the effect of chiral CDs on cytotoxicity reveals that CDs coated with D-Pen, show less cytotoxicity than L-Pen-coated CDs, although generally the cytotoxicity of them is low. The subcellular localization examination reveals that the as-prepared CDs could specifically target and directly illuminate the Golgi apparatus, in spite that no obvious differences are observed between both of them. The discovery could provide a new alternative avenue to trace the cell state by real-time monitoring the Golgi morphology.
研究领域:
生物化学
·
细胞生物学
·
材料科学
✓ 已验证
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Zhirong Geng,Miaomiao Zhang,Binghuan Huang,Xiaohong Zhang,Zhilin Wang
Background Adenosine 5′-triphosphate (ATP) plays an important role in cell metabolism and has been regarded as an indicator of cell survival and damage. Golgi apparatus participates in the signal transduction processes of substance transport, ion homeostasis and stress when extracellular substances enter cells. Till now, there is no fluorescent probe for monitoring Golgi ATP level fluctuation and visualizing the configuration change of the Golgi apparatus during the inhibition of glycolysis. Results Herein, we report the synthesis of a novel water-soluble cationic polythiophene derivative ( PEMTEA) that can be employed as a fluorescent sensor for measuring ATP in the Golgi apparatus. PEMTEA self-assembles into PT-NP nanoparticles in aqueous solution with a diameter of approximately 2 nm. PT-NP displays high sensitivity and superb selectivity towards ATP with a detection limit of 90 nM and a linear detection range from 0 to 3.0 μM. The nanoparticles show low toxicity to HepG2 cells and good photostability in the Golgi apparatus. With the stimulation of Ca 2+ , PT-NP was practically applied to real-time monitor of endogenous ATP levels in the Golgi apparatus through fluorescence microscopy. Finally, we studied the relationship between the concentration of ATP and configuration of the Golgi apparatus during the inhibition of glycolysis using PT-NP . Significance We have demonstrated that PT-NP can not only indicate the fluctuation and distribution of ATP in the Golgi apparatus, but also give the information of the configuration change of the Golgi apparatus at the single-cell level during the inhibition of glycolysis.
研究领域:
细胞生物学
·
生物化学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Xing Zhao,Xi Wu,Ranran Shang,Huachao Chen,Ninghua Tan
The Golgi apparatus (GA) is a vital target for anticancer therapy due to its sensitivity against reactive oxygen species (ROS)-induced oxidative stress that could lead to cell death. In this study, we designed a series of aggregation-induced emission (AIE)-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTI, and TPAPyTM) carrying different ROS with selective GA-targeted ability. The in vitro study showed that TPAPyTZ and TPAPyTC displayed strong AIE characteristics, robust type-I/II ROS production capabilities, specific GA-targeted, high photostability, and high imaging quality. The cell-uptake of TPAPyTZ was found primarily through an energy-dependent caveolae/raft-mediated endocytosis pathway. Remarkably, TPAPyTZ induced GA-oxidative stress, leading to GA fragmentation, downregulation of GM130 expression, and activation of mitochondria caspase-related apoptosis during photodynamic therapy (PDT). In vivo experiments revealed that TPAPyTZ significantly inhibited tumor proliferation under lower-intensity white light irradiation with minimal side effects. Overall, our work presents a promising strategy for designing AIEgens for fluorescence imaging-guided PDT. Additionally, it enriched the collection of GA-targeted leads for the development of cancer theranostics capable of visualizing dynamic changes in the GA during cancer cell apoptosis, which could potentially enable early diagnosis applications in the future. Statement of significance AIE luminogens (AIEgens) are potent phototheranostic agents that can exhibit strong fluorescence emission and enhance ROS production in the aggregate states. In this study, through the precise design of photosensitizers with four different electron-acceptors, we constructed a series of potent AIEgens (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) with strong fluorescence intensity and ROS generation capacity. Among them, TPAPyTZ with an extended π-conjugation displayed the strongest ROS generation ability and anti-tumor activity, resulting in an 88% reduction in tumor weight. Our studies revealed that the enhanced activity of TPAPyTZ may be due to its unique Golgi apparatus (GA)-targeted ability, which causes GA oxidative stress followed by effective cancer cell apoptosis. This unique GA-targeted feature of TPAPyTZ remains rare in the reported AIEgens, which mainly target organelles such as lysosome, mitochondria, and cell membrane. The successful design of a GA-targeted and potent AIEgen could enrich the collection of GA-targeted luminogens, providing a lead theranostic for the further development of fluorescence imaging-guided PDT, and serving as a tool to explore the potential mechanism and discover new GA-specific drug targets.
研究领域:
癌症研究
·
药学
·
生物医学工程
·
材料科学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 9
·e20028
·
IF 4
Qingyuan Cheng,Yiping Duan,Wei Fan,Dongxu Li,Cuiwen Zhu,Tiantian Ma,Jie Liu,Mingxia Yu
Quantum Dots (QDs) modified with branched Polyethylene Glycol-amine (6- or 8-arm PEG-amine) coupled with methoxy PEG (mPEG) hold great promise for in vivo biomedical applications due to a long half-life in blood and negligible toxicity. However, the potential risks regarding their concomitant prolonged co-incubation with cardiovascular and blood cells remains inconclusive. In the present study, the feasible, effective and convenient proliferating-restricted cell line models representing the circulatory system were established to investigate the cellular internalization followed by intracellular outcomes and resulting acute/sub-acute cytotoxicity of the 6-arm PEG-amine/mPEG QDs. We found a dose-, time- and cell type-dependent cellular uptake of the 6-arm PEG-amine/mPEG QDs, which was ten-fold lower compared to the traditional linear PEG-modified counterpart. The QDs entered cells via multiple endocytic pathways and were mostly preserved in Golgi apparatus for at least one week instead of degradation in lysosomes, resulting in a minimal acute cytotoxicity, which is much lower than other types of PEG-modified QDs previously reported. However, a sub-acute cytotoxicity of QDs were observed several days post exposure using the concentrations eliciting no-significant acute cytotoxic effects, which was associated with elevated ROS generation caused by QDs remained inside cells. Finally, a non-cytotoxic concentration of the QDs was identified at the sub-acute cytotoxic level. Our study provided important information for clinical translation of branched PEG-amine/mPEG QDs by elucidating the QDs-cell interactions and toxicity mechanism using the proliferation-restricted cell models representing circulatory system. What's more, we emphasized the indispensability of sub-acute cytotoxic effects in the whole biosafety evaluation process of nanomaterials like QDs.
研究领域:
纳米技术
·
生物医学工程
·
毒理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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