革命性的骨肉瘤治疗一氧化碳和阿霉素协同作用通过介孔二氧化硅纳米颗粒

IF 13.2 1区工程技术 Q1 ENGINEERING, CHEMICAL

Chemical Engineering Journal Pub Date : 2025-06-12 DOI:10.1016/j.cej.2025.164752

Yating Lian, Junyi Zhou, Wei Li, Zhijie Yuan, Minghui Zhong, Tian Wei, Huishan Liang, Shicong Yang, Li Ding, Li-Ming Zhang, Fen Wang

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引用次数: 0

摘要

化疗耐药是骨肉瘤复发转移的主要原因；因此，需要制定有效的治疗措施来逆转化疗耐药。在本研究中，我们设计并合成了硒-杂化可降解中空介孔二氧化硅纳米颗粒（SeNPs），以同时封装阿霉素（DOX）和一氧化碳（CO）释放分子-3 (CORM-3)，并通过二硫键对其表面进行了聚乙二醇（PEG）修饰（SeNP-PEG@DOX-CO）。随后，SeNP-PEG@DOX-CO孵育后，DOX被有效递送到143B细胞中，在高浓度谷胱甘肽（GSH）和活性氧（ROS）的刺激下，CO在线粒体中释放。体外抗癌功能实验和动物实验均证实DOX具有CO-增强抗肿瘤功效，CO可与化疗药物协同抗肿瘤。同时，我们首次提供了CO逆转骨肉瘤化疗耐药的蛋白质组学和代谢组学联合图谱。这项研究揭示了一种革命性的骨肉瘤治疗化疗耐药性的方法。

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The revolutionizing osteosarcoma therapy of carbon monoxide and doxorubicin synergy via mesoporous silica nanoparticles

Chemoresistance is the main cause of recurrence and metastasis in osteosarcoma patients; therefore, efficient therapeutic measures need to be developed to reverse chemoresistance. In this study, we designed and synthesized selenium-hybrid degradable hollow mesoporous silica nanoparticles (SeNPs) to simultaneously encapsulate doxorubicin (DOX) and carbon monoxide (CO)-releasing molecule-3 (CORM-3), and modified their surfaces with polyethylene glycol (PEG) via disulfide bonds (SeNP-PEG@DOX-CO). Subsequently, after incubation with SeNP-PEG@DOX-CO, DOX was effectively delivered into 143B cells, and CO was released in the mitochondria under the stimulation of high concentrations of glutathione (GSH) and reactive oxygen species (ROS). All in vitro anticancer functional experiments and animal experiments confirmed that DOX had CO-enhanced antitumor efficacy and that CO cooperated with chemotherapeutic drugs to resist tumors. Meanwhile, we provided for the first time a combined proteomic and metabolomic landscape of CO reversing chemotherapy resistance in osteosarcoma. This study revealed a revolutionizing osteosarcoma therapy to treat resistance for chemotherapy.

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来源期刊

Chemical Engineering Journal 工程技术-工程：化工

CiteScore

21.70

自引率

9.30%

发文量

6781

审稿时长

2.4 months

期刊介绍： The Chemical Engineering Journal is an international research journal that invites contributions of original and novel fundamental research. It aims to provide an international platform for presenting original fundamental research, interpretative reviews, and discussions on new developments in chemical engineering. The journal welcomes papers that describe novel theory and its practical application, as well as those that demonstrate the transfer of techniques from other disciplines. It also welcomes reports on carefully conducted experimental work that is soundly interpreted. The main focus of the journal is on original and rigorous research results that have broad significance. The Catalysis section within the Chemical Engineering Journal focuses specifically on Experimental and Theoretical studies in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. These studies have industrial impact on various sectors such as chemicals, energy, materials, foods, healthcare, and environmental protection.