机构地区:[1]Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development,Department of Biomedical Engineering,Jinan University,Guangzhou 510632,China [2]Institute of Medicine and Health,Guangdong Academy of Sciences,National Engineering Research Center for Healthcare Devices,Guangdong Key Lab of Medical Electronic Instruments and Polymer Material Products,Guangdong Institute of Medical Instruments,Guangzhou 510500,China [3]Department of Lighl Chemical Engineering,Guangdong Polytechnic,Foshan 528041,China [4]Department of Critical Care Medicine,First Affiliated Hospital,Jinan University,Guangzhou 510632,China [5]MOE Key Laboratory of Tumor Molecular Biology,Jinan University,Guangzhou 510632,China
出 处:《Science China Chemistry》2021年第10期1796-1810,共15页中国科学(化学英文版)
基 金:the National Natural Science Foundation of China(31870943);the Thousands of Doctors(Postdoctoral)Program of Guangdong Academy of Sciences(2019GDASYL-0103015);the Basic and Applied Basic Research Fund of Guangdong Province(2019A1515110663);the Traditional Chinese Medicine Bureau of Guangdong Province(20201109)。
摘 要:The limited intratumoral perfusion of nitric oxide(NO)-carrying nanoparticles into solid tumors caused by the inherent biological barriers in vivo greatly attenuates their generated efficacy. Herein, through entrapping heat-sensitive NO donors(BNN6)on mesoporous polydopamine nanoparticles(M-PDA) and subsequently enveloping with red blood cells membranes, a heatresponsive biomimetic theranostic nanoerythrocyte(M/B@R) is developed to boost NO-based cancer therapy. The reserved intact structure of red blood cells membranes(RBCm) endows M/B@R with superior biosafety and stealth properties for prolonged circulation time and subsequent enhanced tumor accumulation. Once internalized in tumors and excited by nearinfrared light(NIR, 808 nm) irradiation, M/B@R can not only yield plenty of heat for photothermal therapy(PTT) but also achieve the overproduction of NO for highly-efficient NO gas therapy due to its high loading capacity and NIR-absorbing property of M-PDA. The generated NO further ensures the formation of ONOO^(-) which possesses remarkable toxicity to tumor as well as alleviating tumor hypoxia. It is found that M/B@R with NIR as the excitation source can significantly induce synthetic lethality to tumors via the hyperthermia, DNA damage and the ease of tumor hypoxia. Simultaneously, M/B@R also exhibits the potential for bimodal fluorescence and photothermal imaging. The RBCm-camouflaged NO delivery nanoplatform with bimodal imaging capability in this work may provide a new combinatorial paradigm to induce PTT/NO for cancer theranostic applications.
关 键 词:nitric oxide biomimetic nanoerythrocyte PTT/NO synergistic therapy bimodal imaging
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