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已发表论文
基于四氧化三钴的多功能纳米酶重塑肿瘤氧化还原平衡以增强骨肉瘤治疗效果
Authors Yang Y, Gu H, Qin S, Liu J, Xue J, Hu Y, Xue Q, Liu X
Received 25 July 2025
Accepted for publication 7 November 2025
Published 14 November 2025 Volume 2025:20 Pages 13741—13758
DOI https://doi.org/10.2147/IJN.S556295
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Professor Lijie Grace Zhang
Yang Yang,1,2,* Hongmei Gu,3,* Shuheng Qin,4,* Jiajia Liu,2 Jianhua Xue,2 Yong Hu,4 Qiang Xue,3 Xianchen Liu3
1Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China; 2Department of Chemistry, School of Science, China Pharmaceutical University, Nanjing, Jiangsu, 226001, People’s Republic of China; 3Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China; 4College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210023, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xianchen Liu, Email xianchenliunt@sina.com Qiang Xue, Email ntxueqiang@163.com
Background: Developing nanodrugs with passive targeting capabilities that can effectively overcome the oxidative-redox homeostasis-inhibiting microenvironment of tumors offers new insights into the precise treatment of osteosarcoma.
Methods: CoFe2O4 nanoparticles were synthesized via the hydrothermal method and modified with polyethylene glycol 4000 on their surface, obtaining CF@P nanozymes with multi-catalytic activities similar to catalase (CAT), peroxidase (POD), oxidase (OD), and glutathione peroxidase (GPx). These nanozymes could overcome the hypoxic microenvironment and redox homeostasis in osteosarcoma treatment.
Results: CF@P has a size of approximately 100 nm and can stably exist under physiological conditions. It exhibits excellent photothermal effects under near-infrared II (1064 nm) laser irradiation, synergistically enhancing its catalytic activity. CF@P alleviates hypoxia by decomposing endogenous H2O2 within tumors to generate oxygen and hydroxyl radicals (·OH). Meanwhile, it consumes reduced glutathione (GSH) within tumors, inducing ferroptosis and apoptosis. CF@P exhibits low toxicity to normal cells (HUVEC) and selective killing ability against osteosarcoma cells (U2OS). In vivo, it accumulates in tumor tissues via the enhanced permeability and retention (EPR) effect, significantly inhibiting tumor growth in combination with photothermal therapy without causing significant organ toxicity, thereby prolonging the survival of tumor-bearing mice.
Conclusion: The CF@P nanozyme integrates the properties of multi-enzyme catalysis and photothermal therapy, disrupting the oxidative-redox homeostasis of tumor tissues, generating highly toxic hydroxyl radicals, and efficiently inducing apoptosis in osteosarcoma cells. This approach provides a new, efficient, and safe strategy for the precise treatment of hypoxic solid tumors like osteosarcoma.
Keywords: cobalt ferrite (CoFe2O4), nanozyme, reactive oxygen species, photothermal effect, osteosarcoma
1Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China; 2Department of Chemistry, School of Science, China Pharmaceutical University, Nanjing, Jiangsu, 226001, People’s Republic of China; 3Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China; 4College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210023, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xianchen Liu, Email xianchenliunt@sina.com Qiang Xue, Email ntxueqiang@163.com
Background: Developing nanodrugs with passive targeting capabilities that can effectively overcome the oxidative-redox homeostasis-inhibiting microenvironment of tumors offers new insights into the precise treatment of osteosarcoma.
Methods: CoFe2O4 nanoparticles were synthesized via the hydrothermal method and modified with polyethylene glycol 4000 on their surface, obtaining CF@P nanozymes with multi-catalytic activities similar to catalase (CAT), peroxidase (POD), oxidase (OD), and glutathione peroxidase (GPx). These nanozymes could overcome the hypoxic microenvironment and redox homeostasis in osteosarcoma treatment.
Results: CF@P has a size of approximately 100 nm and can stably exist under physiological conditions. It exhibits excellent photothermal effects under near-infrared II (1064 nm) laser irradiation, synergistically enhancing its catalytic activity. CF@P alleviates hypoxia by decomposing endogenous H2O2 within tumors to generate oxygen and hydroxyl radicals (·OH). Meanwhile, it consumes reduced glutathione (GSH) within tumors, inducing ferroptosis and apoptosis. CF@P exhibits low toxicity to normal cells (HUVEC) and selective killing ability against osteosarcoma cells (U2OS). In vivo, it accumulates in tumor tissues via the enhanced permeability and retention (EPR) effect, significantly inhibiting tumor growth in combination with photothermal therapy without causing significant organ toxicity, thereby prolonging the survival of tumor-bearing mice.
Conclusion: The CF@P nanozyme integrates the properties of multi-enzyme catalysis and photothermal therapy, disrupting the oxidative-redox homeostasis of tumor tissues, generating highly toxic hydroxyl radicals, and efficiently inducing apoptosis in osteosarcoma cells. This approach provides a new, efficient, and safe strategy for the precise treatment of hypoxic solid tumors like osteosarcoma.
Keywords: cobalt ferrite (CoFe2O4), nanozyme, reactive oxygen species, photothermal effect, osteosarcoma