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

• Published in: International journal of biological macromolecules Vol. 278; no. Pt 1; p. 134187
• Main Authors: Fan, Zhiyuan, Shao, Yuheng, Jiang, Xiao, Zhou, Jinglan, Yang, Liang, Chen, Haitao, Liu, Wentao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chitosan - chemistry; Chitosan - pharmacology; Chitosan-polymersome; Drug Liberation; Gastric cancer cells; Humans; Infrared Rays; Melatonin - chemistry; Melatonin - pharmacology; Nanoparticles - chemistry; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; TOR Serine-Threonine Kinases - metabolism; Up-conversion nanoparticles; Up-conversion nanoparticles; Gastric cancer cells; Chitosan-polymersome
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.134187

In this study, a formulation of NaGdF4:Tm/Er@NaGdF4 (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 NaGdF4:Tm/Er@NaGdF4 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 (IC50 = 0.096 μM) and AGS (IC50 = 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. •Merging the chemo/phototherapy effect by melatonin-NaGdF4:Tm/Er@NaGdF4 UCNPs coated with chitosan-polymersome.•NIR irradiated chitosan-polymersome coated UCNPs eradicated 53.84 % of HGC27 and 47.71 % of AGS.•NIR irradiated chitosan-polymersome delivered superior biocompatibility against HUVECs (88.7 %) and L929 (93 %).•The formulation promoted apoptosis by regulating ROS/PI3K/Akt/mTOR pathway