ABSTRACT
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⯱â¯3.56â¯nm) and a low zeta potential (17.91â¯mV). Furthermore, drug release profiles demonstrated superior melatonin drug release (79.78â¯%) at pHâ¯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 (IC50â¯=â¯0.096⯵M) and AGS (IC50â¯=â¯0.16⯵M) 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⯵g/mL) reveal a notable cell viability of 88.7â¯% and 93â¯% 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.