Source abstract
Abstract
Ferroptosis, a unique iron-dependent mode of cell death, has been identified as a potential treatment for glioblastoma (GBM). Dihydroartemisinin (DHA) is a ferroptosis inducer with cytotoxicity that is strongly dependent on intracellular Fe 2+ levels. However, the effectiveness of DHA is limited by low levels of Fe 2+ in tumor cells. To address this issue, a facile strategy was developed by combining near-infrared (NIR)-induced ferrous ion regeneration with DHA in a nanocomposite (ApoE-UPGs-DHA). This nanocomposite synergistically enhanced ferroptosis and offered highly efficient GBM treatment. ApoE-UPGs-DHA were prepared by loading upconversion nanoparticles (UCNPs) and DHA into micelles and subsequently attaching the peptide apolipoprotein E to enable penetration of the blood-brain barrier (BBB) and targeted treatment of GBM. NIR irradiation was applied to induce the regeneration of Fe 2+ from Fe 3+ mediated by ApoE-UPGs-DHA, thereby promoting ferroptosis in G422 glioma cells. Characterization studies confirmed the successful preparation of ApoE-UPGs-DHA, which had a diameter of 82.3 ± 5.8 nm. The nanocomposite demonstrated good GBM targeting ability in vivo and enhanced uptake by the G422 cells in vitro. ApoE-UPGs-DHA were toxic to G422 glioma cells, and this toxicity was further enhanced by NIR irradiation. Mechanistic studies revealed that ApoE-UPGs-DHA treatment led to a decrease in the intracellular Fe 2+ concentration due to the Fenton-like reaction induced by DHA and Fe 2+ . NIR irradiation was transformed into UV light by ApoE-UPGs-DHA, and then, the Fe 3+ generated by the Fenton reaction was photoreduced to Fe 2+ by UV light. The replenished Fe 2+ significantly promoted the generation of lipid peroxides (LPOs), leading to enhanced ferroptosis and toxicity to ApoE-UPGs-DHA-treated G422 glioma cells. Herein, an NIR-responsive Fe 2+ -regenerating nanocomposite was successfully prepared to enhance ferroptosis in G422 glioma cells, suggesting a promising alternative GBM treatment strategy.
Source: openalex_inverted_index · Quality: baseline
Affiliations
Medical School, Southeast University, No. 87, Dingjiaqiao, Nanjing, Jiangsu 210003, China
Department of Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, China
Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, No. 87, Dingjiaqiao, Nanjing, Jiangsu 210003, China
Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210016, China
Funding
the Provincial Foundation of Jiangsu Province · the Key Research and Development Program of Jiangsu Province · the Key Project Foundation of Jiangsu Health and Health Committee