超声激活纳米疫苗可扩增双模态活性氧用于癌症超声免疫治疗

IF 11.5 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yiming Liu , Guangzhe Li , Guibin Wang , Yang Wang , Jianlong Su , Zhihao Wu , Ruimin Wang , Xiaomai Zhang , Jinrong Li , Guanyi Zhang , Yuxuan Zhang , Xu Wang , Yuanhang Yao , Mingrui Bai , Ruoshi Wang , Lei Wang , Jingdong Zhang , Kun Shao
{"title":"超声激活纳米疫苗可扩增双模态活性氧用于癌症超声免疫治疗","authors":"Yiming Liu ,&nbsp;Guangzhe Li ,&nbsp;Guibin Wang ,&nbsp;Yang Wang ,&nbsp;Jianlong Su ,&nbsp;Zhihao Wu ,&nbsp;Ruimin Wang ,&nbsp;Xiaomai Zhang ,&nbsp;Jinrong Li ,&nbsp;Guanyi Zhang ,&nbsp;Yuxuan Zhang ,&nbsp;Xu Wang ,&nbsp;Yuanhang Yao ,&nbsp;Mingrui Bai ,&nbsp;Ruoshi Wang ,&nbsp;Lei Wang ,&nbsp;Jingdong Zhang ,&nbsp;Kun Shao","doi":"10.1016/j.jconrel.2025.114285","DOIUrl":null,"url":null,"abstract":"<div><div>Insufficient reactive oxygen species (ROS), including limited ROS bioactivity and poor accumulation efficiency inside tumor cells, remain a major barrier to the effectiveness of sonodynamic therapy (SDT). Among ROS types, hydroxyl radical (·OH) displays superior killing efficiency compared to singlet oxygen (<sup>1</sup>O₂), while diminishing oxygen reliance. Nevertheless, most existing small molecule sonosensitizers exhibit <sup>1</sup>O<sub>2</sub>-predominance under ultrasound (US). In this study, we discovered that RB-Biotin, a derivative of the classical <sup>1</sup>O<sub>2</sub> sonosensitizer Rose Bengal (RB), remarkably augmented ·OH production without compromising <sup>1</sup>O<sub>2</sub> yield under US irradiation. The dual-modal ROS generation mechanism was elucidated by computational studies of density functional theory (DFT). RB-Biotin was further loaded onto MnO<sub>2</sub>-based nanocarriers to obtain the ultrasound-enabled nanovaccines, BMRP. The MnO<sub>2</sub> scaffold not only transformed the endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into oxygen to fuel <sup>1</sup>O<sub>2</sub> production by RB-Biotin, but also inhibited ROS depletion by blocking intracellular glutathione (GSH), creating a dual-modal ROS “reservoir” within tumor cells. In a mouse hepatocellular carcinoma (HCC) model, BMRP demonstrated a potent sono-immune therapeutic effect through synergistic dual-modal ROS (<sup>1</sup>O<sub>2</sub> and ·OH) amplification and locally released Mn<sup>2+</sup>-favored immune activation, leading to remarkable tumor regression and robust anti-tumor immune responses. This work represents a paradigm shift in SDT by transitioning from mono-modal to dual-modal ROS generation, leveraging the complementary oxidative mechanisms of <sup>1</sup>O<sub>2</sub> and ·OH to improve SDT efficacy. By integrating the strengths of RB-Biotin and MnO<sub>2</sub> nanocarriers, this approach not only overcomes intrinsic limitations of conventional SDT, but also expands the application of ultrasound-driven cancer therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114285"},"PeriodicalIF":11.5000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ultrasound-activatable nanovaccines amplify dual-modal ROS for cancer sono-immunotherapy\",\"authors\":\"Yiming Liu ,&nbsp;Guangzhe Li ,&nbsp;Guibin Wang ,&nbsp;Yang Wang ,&nbsp;Jianlong Su ,&nbsp;Zhihao Wu ,&nbsp;Ruimin Wang ,&nbsp;Xiaomai Zhang ,&nbsp;Jinrong Li ,&nbsp;Guanyi Zhang ,&nbsp;Yuxuan Zhang ,&nbsp;Xu Wang ,&nbsp;Yuanhang Yao ,&nbsp;Mingrui Bai ,&nbsp;Ruoshi Wang ,&nbsp;Lei Wang ,&nbsp;Jingdong Zhang ,&nbsp;Kun Shao\",\"doi\":\"10.1016/j.jconrel.2025.114285\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Insufficient reactive oxygen species (ROS), including limited ROS bioactivity and poor accumulation efficiency inside tumor cells, remain a major barrier to the effectiveness of sonodynamic therapy (SDT). Among ROS types, hydroxyl radical (·OH) displays superior killing efficiency compared to singlet oxygen (<sup>1</sup>O₂), while diminishing oxygen reliance. Nevertheless, most existing small molecule sonosensitizers exhibit <sup>1</sup>O<sub>2</sub>-predominance under ultrasound (US). In this study, we discovered that RB-Biotin, a derivative of the classical <sup>1</sup>O<sub>2</sub> sonosensitizer Rose Bengal (RB), remarkably augmented ·OH production without compromising <sup>1</sup>O<sub>2</sub> yield under US irradiation. The dual-modal ROS generation mechanism was elucidated by computational studies of density functional theory (DFT). RB-Biotin was further loaded onto MnO<sub>2</sub>-based nanocarriers to obtain the ultrasound-enabled nanovaccines, BMRP. The MnO<sub>2</sub> scaffold not only transformed the endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into oxygen to fuel <sup>1</sup>O<sub>2</sub> production by RB-Biotin, but also inhibited ROS depletion by blocking intracellular glutathione (GSH), creating a dual-modal ROS “reservoir” within tumor cells. In a mouse hepatocellular carcinoma (HCC) model, BMRP demonstrated a potent sono-immune therapeutic effect through synergistic dual-modal ROS (<sup>1</sup>O<sub>2</sub> and ·OH) amplification and locally released Mn<sup>2+</sup>-favored immune activation, leading to remarkable tumor regression and robust anti-tumor immune responses. This work represents a paradigm shift in SDT by transitioning from mono-modal to dual-modal ROS generation, leveraging the complementary oxidative mechanisms of <sup>1</sup>O<sub>2</sub> and ·OH to improve SDT efficacy. By integrating the strengths of RB-Biotin and MnO<sub>2</sub> nanocarriers, this approach not only overcomes intrinsic limitations of conventional SDT, but also expands the application of ultrasound-driven cancer therapy.</div></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":\"388 \",\"pages\":\"Article 114285\"},\"PeriodicalIF\":11.5000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365925008983\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365925008983","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

摘要

活性氧(ROS)不足,包括活性氧生物活性有限和肿瘤细胞内积累效率差,仍然是影响声动力治疗(SDT)有效性的主要障碍。在活性氧类型中,羟基自由基(·OH)比单线态氧(o₂)表现出更强的杀伤效率,同时降低了对氧的依赖。然而,大多数现有的小分子声敏剂在超声下表现出102 -优势(US)。在这项研究中,我们发现RB- biotin是经典的1O2声敏剂Rose Bengal (RB)的衍生物,在美国辐照下显著增加·OH的产生,而不影响1O2的产率。通过密度泛函理论(DFT)的计算研究阐明了双模态ROS的产生机制。将rb -生物素进一步装载到二氧化锰基纳米载体上,以获得超声激活的纳米疫苗BMRP。MnO2支架不仅将内源性过氧化氢(H2O2)转化为氧气,为rb -生物素产生1O2提供燃料,而且还通过阻断细胞内谷胱甘肽(GSH)抑制ROS的消耗,在肿瘤细胞内形成双峰ROS“库”。在小鼠肝细胞癌(HCC)模型中,BMRP通过协同双峰ROS (1O2和·OH)扩增和局部释放Mn2+有利的免疫激活,显示出强大的声免疫治疗作用,导致显著的肿瘤消退和强大的抗肿瘤免疫应答。这项工作代表了SDT从单模态到双模态ROS生成的范式转变,利用1O2和·OH的互补氧化机制来提高SDT疗效。该方法结合了rb -生物素和MnO2纳米载体的优势,不仅克服了常规SDT的固有局限性,而且扩大了超声驱动癌症治疗的应用范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ultrasound-activatable nanovaccines amplify dual-modal ROS for cancer sono-immunotherapy

Ultrasound-activatable nanovaccines amplify dual-modal ROS for cancer sono-immunotherapy

Ultrasound-activatable nanovaccines amplify dual-modal ROS for cancer sono-immunotherapy
Insufficient reactive oxygen species (ROS), including limited ROS bioactivity and poor accumulation efficiency inside tumor cells, remain a major barrier to the effectiveness of sonodynamic therapy (SDT). Among ROS types, hydroxyl radical (·OH) displays superior killing efficiency compared to singlet oxygen (1O₂), while diminishing oxygen reliance. Nevertheless, most existing small molecule sonosensitizers exhibit 1O2-predominance under ultrasound (US). In this study, we discovered that RB-Biotin, a derivative of the classical 1O2 sonosensitizer Rose Bengal (RB), remarkably augmented ·OH production without compromising 1O2 yield under US irradiation. The dual-modal ROS generation mechanism was elucidated by computational studies of density functional theory (DFT). RB-Biotin was further loaded onto MnO2-based nanocarriers to obtain the ultrasound-enabled nanovaccines, BMRP. The MnO2 scaffold not only transformed the endogenous hydrogen peroxide (H2O2) into oxygen to fuel 1O2 production by RB-Biotin, but also inhibited ROS depletion by blocking intracellular glutathione (GSH), creating a dual-modal ROS “reservoir” within tumor cells. In a mouse hepatocellular carcinoma (HCC) model, BMRP demonstrated a potent sono-immune therapeutic effect through synergistic dual-modal ROS (1O2 and ·OH) amplification and locally released Mn2+-favored immune activation, leading to remarkable tumor regression and robust anti-tumor immune responses. This work represents a paradigm shift in SDT by transitioning from mono-modal to dual-modal ROS generation, leveraging the complementary oxidative mechanisms of 1O2 and ·OH to improve SDT efficacy. By integrating the strengths of RB-Biotin and MnO2 nanocarriers, this approach not only overcomes intrinsic limitations of conventional SDT, but also expands the application of ultrasound-driven cancer therapy.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Controlled Release
Journal of Controlled Release 医学-化学综合
CiteScore
18.50
自引率
5.60%
发文量
700
审稿时长
39 days
期刊介绍: The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信