Perturbation of hyperthermia resistance in gastric cancer by hyperstimulation of autophagy using artemisinin-protected iron-oxide nanoparticles.
| Autor: | Attri K; Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India diptiman@thapar.edu +91-8196949843.; TIET-VT Centre of Excellence for Emerging Materials, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India., Chudasama B; Department of Physics and Material Sciences, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India bnchudasama@thapar.edu +91-9781966136.; TIET-VT Centre of Excellence for Emerging Materials, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India., Mahajan RL; Department of Mechanical Engineering, Department of Materials Science & Engineering, Virginia Tech Blacksburg VA 24061 USA mahajanr@vt.edu +1-5402312597.; TIET-VT Centre of Excellence for Emerging Materials, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India., Choudhury D; Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India diptiman@thapar.edu +91-8196949843.; TIET-VT Centre of Excellence for Emerging Materials, Thapar Institute of Engineering and Technology Patiala 147004 Punjab India. |
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| Jazyk: | angličtina |
| Zdroj: | RSC advances [RSC Adv] 2024 Oct 29; Vol. 14 (47), pp. 34565-34577. Date of Electronic Publication: 2024 Oct 29 (Print Publication: 2024). |
| DOI: | 10.1039/d4ra05611f |
| Abstrakt: | In a bid to overcome hyperthermia resistance, a major obstacle in cancer treatment, this study explores manipulating autophagy, a cellular recycling mechanism, within the context of gastric cancer. We designed artemisinin-protected magnetic iron-oxide nanoparticles (ART-MNPs) to hyperactivate autophagy, potentially sensitizing cancer cells to hyperthermia. The synthesized ART-MNPs exhibited magnetic properties and the capability of raising the temperature by 7 °C at 580.3 kHz. Importantly, ART-MNPs displayed significant cytotoxicity against human gastric cancer cells (AGS), with an IC50 value of 1.9 μg mL -1 , demonstrating synergistic effects compared to either MNPs or ART treatment alone (IC50 for MNPs is 9.7 μg mL -1 and for ART is 9.4 μg mL -1 respectively). Combination index studies further supported this synergy. Mechanistic analysis revealed a significant increase in autophagy level (13.58- and 15.08-fold increase compared to artemisinin and MNPs, respectively) upon ART-MNP treatment, suggesting that this hyperactivation is responsible for hyperthermia sensitization and minimized resistance (as evidenced by changes in viability compared to control under hyperthermic conditions). This work offers a promising strategy to modulate autophagy and overcome hyperthermia resistance, paving the way for developing hyperthermia as a standalone therapy for gastric cancer. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.) |
| Databáze: | MEDLINE |
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