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Cytotoxic effects of NIR responsive chitosan-polymersome layer coated melatonin-upconversion nanoparticles on HGC27 and AGS gastric cancer cells: Role of the ROS/PI3K/Akt/mTOR signaling pathway.
- Source :
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International journal of biological macromolecules [Int J Biol Macromol] 2024 Oct; Vol. 278 (Pt 1), pp. 134187. Date of Electronic Publication: 2024 Aug 03. - Publication Year :
- 2024
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Abstract
- In this study, a formulation of NaGdF <subscript>4</subscript> :Tm/Er@NaGdF <subscript>4</subscript> (core@shell) UCNPs loaded with melatonin drug was synthesized. The novel melatonin-loaded UCNPs were then encapsulated within NIR-responsive biopolymeric chitosan (CS) based polymersome and investigated against gastric cancer (HGC27 & AGS) cells. The photolysis of the ONB moiety and disruption of the disulfide linkage in the polymersome induced by NIR light facilitated by the NaGdF <subscript>4</subscript> :Tm/Er@NaGdF <subscript>4</subscript> UCNPs and GSH results in an increased release of melatonin drug. The DLS and zeta potential measurements exhibit a reduced particle size (21.9 ± 3.56 nm) and a low zeta potential (17.91 mV). Furthermore, drug release profiles demonstrated superior melatonin drug release (79.78 %) at pH 5.0 for CS-polymersome-coated melatonin-UCNPs resembling the Hixson-Crowell model. Remarkably, CS-polymersome-coated melatonin-UCNPs exhibit excellent anti-proliferative properties for HGC27 (IC <subscript>50</subscript>  = 0.096 μM) and AGS (IC <subscript>50</subscript>  = 0.16 μM) cancer cells. The flow cytometry data demonstrate a significant elevation in ROS levels which promoted cell death in both HGC-27 and AGS cells. The observed cell mortality in HGC-27 and AGS cells is primarily caused by the destruction of the nucleus, mtDNA, rupture of disulfide (R-S-S-R) bonds, and nuclear DNA. Contrarily, L929 and HUVECs cells incubated with CS-polymersome coated melatonin-UCNPs (100 μg/mL) reveal a notable cell viability of 88.7 % and 93 % indicating superior biocompatibility. The western blotting analysis revealed the induction of autophagy by CS-polymersome-coated melatonin-UCNPs which subsequently led to apoptosis by regulating the ROS/PI3K/Akt/mTOR molecular signaling pathway.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Cell Line, Tumor
Infrared Rays
Apoptosis drug effects
Cell Proliferation drug effects
Drug Liberation
Cell Survival drug effects
Melatonin pharmacology
Melatonin chemistry
Chitosan chemistry
Chitosan pharmacology
TOR Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Stomach Neoplasms drug therapy
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Nanoparticles chemistry
Phosphatidylinositol 3-Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 278
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 39098665
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2024.134187