Tracking the Cellular Degradation of Silver Nanoparticles: Development of a Generic Kinetic Model

ACS Nano, Journal Year: 2024, Volume and Issue: 18(20), P. 13308 - 13321

Published: May 8, 2024

Understanding the degradation of nanoparticles (NPs) after crossing cell plasma membrane is crucial in drug delivery designs and cytotoxicity assessment. However, key factors controlling degradable kinetics remain unclear due to absence a quantification model. In this study, subcellular imaging silver (AgNPs) was used determine intracellular transfer AgNPs, single particle ICP-MS utilized track process. A cellular kinetic model subsequently developed describe uptake, transfer, behaviors AgNPs. Our demonstrated that efficiency AgNPs much higher than determined by mimicking testing, NPs highly influenced factors. Specifically, deficiencies Ca or Zn primarily decreased dissolution NPs, while deficiency also resulted retardation NP transfer. The biological significance these parameters strongly revealed. indicated majority internalized dissolved, with resulting ions being rapidly depurated. release Ag largely dependent on microvesicle-mediated route. By changing coating size results suggested into process, whereas affected kinetics. Overall, our provides valuable tool for understanding predicting impacts physicochemical properties ambient environment nanotoxicity therapeutic efficacy.

Language: Английский

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Membrane drug transporters in cancer: From chemoresistance mechanism to therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(2), P. 189272 - 189272

Published: Jan. 23, 2025

Language: Английский

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Multifaceted Sulfonamide-Derived Thiosemicarbazones: Combining Metal Chelation and Carbonic Anhydrases Inhibition in Anticancer Therapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1225 - 1225

Published: Jan. 30, 2025

The selective inhibition of key enzymes, such as carbonic anhydrases (CAs IX and XII), which are overexpressed in cancer tissues, has emerged a promising strategy research. However, multitarget approach is often preferred to achieve enhanced therapeutic outcomes. In this study, aryl sulfonamides were conjugated with thiosemicarbazone moiety enable dual functionality: the CAs chelation metal cations. Several structural factors systematically modified, including position sulfonamido group, length linker, nature aromatic residue, type substituents. Tumor-associated XII was evaluated using stopped-flow CO2 hydrase assay, constants (Ki) determined. most compounds further analyzed through molecular docking simulations. Metal capabilities UV–Vis spectroscopy, while antiproliferative activities measured sulforhodamine B (SBR) assay. Additionally, holotomographic 3D microscopy employed investigate mechanisms cell death. Sulfonamido-derived Schiff bases synthesized three-step procedure that did not require column chromatography purification: (1) isothiocyanation amino-sulfonamides, (2) nucleophilic addition hydrazine, (3) acid-promoted condensation different aldehydes (benzaldehydes or pyridine-2-carboxaldehyde). exhibited low nanomolar submicromolar range, selectivity largely influenced by features. Notably, m-sulfonamide derivative 5b, bearing pyridin-2-yl demonstrated potent CA (Ki = 4.9 nM) 5.6 nM). it efficiently chelated Fe2+, Fe3+, Cu2+ showed activity (GI50 4.5–10 µM). Mechanistic studies revealed apoptosis involved its mode action. Therefore, synergistic integration thiosemicarbazones represents an effective for development multimodal anticancer agents.

Language: Английский

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Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Breast cancer is the most commonly diagnosed worldwide. Metal metabolism pivotal for regulating cell fate and drug sensitivity in breast cancer. Iron copper are essential metal ions critical maintaining cellular function. The accumulation of iron triggers distinct death pathways, known as ferroptosis cuproptosis, respectively. Ferroptosis characterized by iron-dependent lipid peroxidation, while cuproptosis involves copper-induced oxidative stress. They increasingly recognized promising targets development anticancer drugs. Recently, compelling evidence demonstrated that interplay between plays a crucial role progression. This review elucidates converging pathways Moreover, we examined value genes associated with clinical diagnosis treatment cancer, mainly outlining potential co-targeting approach. Lastly, delve into current challenges limitations this strategy. In general, offers an overview interaction offering valuable perspectives further research treatment.

Language: Английский

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Metal-Dependent Cell Death in Renal Fibrosis: Now and in the Future

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13279 - 13279

Published: Dec. 11, 2024

Renal fibrosis is a common final pathway underlying nearly almost all progressive kidney diseases. Metal ions are essential trace elements in organisms and involved important physiological activities. However, aberrations intracellular metal ion metabolism may disrupt homeostasis, causing cell death increasing susceptibility to various Accumulating evidence suggests complex association between metal-dependent renal fibrosis. In this article, we provide comprehensive overview of the specific molecular mechanisms their crosstalk, up-to-date supporting role fibrosis, therapeutic targeting strategies, research needs, aiming offer rationale for future clinical treatment

Language: Английский

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