Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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外文摘要：Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatio-temporal release precision,associated with gas therapy.In this study,we developed a series of photoac-tivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine scaffold.Under the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion lumines-cence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation energy.We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O2·-produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO-)gener-ated from the co-existence of NO and O2·-.After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target mitochondria.Under an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mito-chondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tu-mor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging.Collectively,this versatile strategy defines the targeted RNS-mediated cancer therapy.

外文关键词：

Near infraredPhoto-triggeredMitochondrionUpconversion luminescent bioimagingPeroxynitriteNanogeneratorGas therapyIn vivo

作者：

Hui Yu、Aliya Tiemuer、Xufeng Yao、Mingyuan Zuo、Hai-Yan Wang、Yi Liu、Xiaoyuan Chen

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作者单位：

Department of Biomedical Engineering,School of Engineering,China Pharmaceutical University,Nanjing 211198,China

School of Mechanical Engineering,Southeast University,Nanjing 211189,China

Departments of Diagnostic Radiology,Surgery,Chemical and Biomolecular Engineering,and Biomedical Engineering,Yong Loo Lin School of Medicine and College of Design and Engineering,National University of Singapore,Singapore 119074,Singapore

Clinical Imaging Research Centre,Centre for Translational Medicine,Yong Loo Lin School of Medicine,National University of Singapore,Singapore 117599,Singapore

Nanomedicine Translational Research Program,Yong Loo Lin School of Medicine,National University of Singapore,Singa

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基金：

国家自然科学基金the"Double First-Class"University ProjectJiangsu Funding Program for Excellent Postdoctoral TalentNational University of SingaporeNational University of SingaporeNational University of SingaporeNational Medical Research CouncilNational Medical Research Council新加坡教育部项目National Research Foundation

项目编号：

82272148CPUQNJC22-032022ZB301NUHSRO/2020/133/Startup/08NUHSRO/2023/008/NUSMed/TCE/LOANUHSRO/2021/034/TRP/09/NanomedicineMOH-OFIRG23jan-0005CG21APR1005MOE-000387-00NRF-000352-00

出版年：

2024

DOI：

10.1016/j.apsb.2023.08.019

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(1)

参考文献量52