Department of Breast Surgery, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Department of Radiation Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Int J Biol Macromol. 2024 Oct;278(Pt 1):134187. doi: 10.1016/j.ijbiomac.2024.134187. Epub 2024 Aug 3.
In this study, a formulation of NaGdF:Tm/Er@NaGdF (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:Tm/Er@NaGdF 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 = 0.096 μM) and AGS (IC = 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.
在这项研究中，合成了负载褪黑素药物的 NaGdF:Tm/Er@NaGdF（核@壳）上转换纳米粒子（UCNPs）制剂。然后，将新型负载褪黑素的 UCNPs 封装在近红外响应性生物聚合物壳聚糖（CS）聚合物泡囊内，并对其进行了胃（HGC27 和 AGS）癌细胞的研究。NaGdF:Tm/Er@NaGdF UCNPs 和 GSH 通过光解 ONB 部分和破坏聚合物泡囊中的二硫键，在近红外光的作用下，导致褪黑素药物的释放增加。动态光散射（DLS）和 zeta 电位测量显示，粒径减小（21.9±3.56nm），zeta 电位降低（17.91mV）。此外，药物释放曲线表明，在 pH 5.0 下，CS 聚合物泡囊包裹的褪黑素-UCNPs 具有更好的褪黑素药物释放（79.78%），类似于 Hixson-Crowell 模型。值得注意的是，CS 聚合物泡囊包裹的褪黑素-UCNPs 对 HGC27（IC=0.096μM）和 AGS（IC=0.16μM）癌细胞具有优异的抗增殖特性。流式细胞术数据显示，ROS 水平显著升高，促进了 HGC-27 和 AGS 细胞的死亡。在 HGC-27 和 AGS 细胞中观察到的细胞死亡率主要是由于细胞核、mtDNA、二硫键（R-S-S-R）断裂和核 DNA 的破坏。相反，孵育 CS 聚合物泡囊包裹的褪黑素-UCNPs（100μg/mL）的 L929 和 HUVECs 细胞显示出显著的细胞活力，分别为 88.7%和 93%，表明其具有优异的生物相容性。Western blot 分析显示，CS 聚合物泡囊包裹的褪黑素-UCNPs 诱导自噬，随后通过调节 ROS/PI3K/Akt/mTOR 分子信号通路诱导细胞凋亡。
