Low Intensity Focused Ultrasound Ignited "Deep-Penetration Nanobomb" (DPNB) for Tetramodal Imaging Guided Hypoxia-Tolerant Sonodynamic Therapy Against Hypoxic Tumors

作者全名："Luo, Yuanli; Qiao, Bin; Yang, Chao; Zhang, Ping; Xie, Zhuoyan; Cao, Jin; Yang, Anyu; Xiang, Qinyanqiu; Ran, Haitao; Wang, Zhigang; Hao, Lan; Cao, Yang; Zhou, Zhiyi; Ren, Jianli"

作者地址："[Luo, Yuanli; Qiao, Bin; Zhang, Ping; Xie, Zhuoyan; Cao, Jin; Yang, Anyu; Xiang, Qinyanqiu; Ran, Haitao; Wang, Zhigang; Hao, Lan; Cao, Yang; Ren, Jianli] Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Yang, Chao] Chongqing Gen Hosp, Radiol Dept, Chongqing 400014, Peoples R China; [Zhou, Zhiyi] Chongqing Gen Hosp, Gen Practice Dept, Chongqing 400014, Peoples R China"

通信作者："Ren, JL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Zhou, ZY (通讯作者)，Chongqing Gen Hosp, Gen Practice Dept, Chongqing 400014, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000862748000001

JCR分区：Q1

影响因子：8

年份：2022

卷号：17

期号：　

开始页：4547

结束页：4565

文献类型：Article

关键词：tetramodal imaging; low intensity focused ultrasound; sonodynamic therapy; deep-penetration; hypoxic tumors

摘要："Background: Sonodynamic therapy (SDT) has been regarded as a novel therapeutic modality for killing tumors. However, the hypoxic tumor microenvironment, especially deep-seated tumors distant from blood vessels, severely restricts therapeutic efficacy due to the oxygen-dependent manner of SDT.Methods: Herein, we report a novel ultrasonic cavitation effect-based therapeutic modality that is able to facilitate the hypoxia-tolerant SDT for inducing hypoxic tumor death. A tLyP-1 functionalized liposomes is fabricated, composed of hematoporphyrin monomethyl ether gadolinium as the sonosentizer and perfluoropentane (PFP) as the acoustic environment regulator. Moreover, the tLyP-1 functioned liposomes could achieve active tumor homing and effective deep-penetrating into hypoxic tumors. Upon low intensity focused ultrasound (LIFU) irradiation, the acoustic droplet vaporization effect of PFP induced fast liquid-to-gas transition and quick bubbles explosion to generate hydroxyl radicals, efficiently promoting cell death in both normoxic and hypoxic microenviron-ment (acting as deep-penetration nanobomb, DPNB).Results: The loading of PFP is proved to significantly enhance the therapeutic efficacy of hypoxic tumors. In particular, these DPNB can also act as ultrasound, photoacoustic, magnetic resonance, and near-infrared fluorescence tetramodal imaging agents for guiding the therapeutic process.Conclusion: This study is the first report involving that liquid-to-gas transition based SDT has the potential to combat hypoxic tumors."

基金机构："National Natural Science Foundation of China [82171946, 81873901]; Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission [cstc2019jcyj-zdxmX0020]; project of China Postdoctoral Science Foundation [2021M690171]; Guangdong Basic and Applied Basic Research Foundation [2021A1515110102]; CQMU Program for Youth Innovation in Future Medicine [W0026]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [KR2019G001]; Chongqing Science and Health Joint Medical Research Project-Young and Middle-aged High-level Talent Project [2020GDRC011]; Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing [20190112]; Chongqing General Hospital Medical Science and Technology Innovation Project [2019ZDXM08]; High-level Medical Reserved Personnel Training Project of Chongqing"

基金资助正文："The authors sincerely grateful for the financial supports from the National Natural Science Foundation of China (Grant No. 82171946, 81873901), Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission (Grant No. cstc2019jcyj-zdxmX0020), the project of China Postdoctoral Science Foundation (2021M690171), Guangdong Basic and Applied Basic Research Foundation (2021A1515110102), High-level Medical Reserved Personnel Training Project of Chongqing, CQMU Program for Youth Innovation in Future Medicine (W0026), Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (KR2019G001), Chongqing Science and Health Joint Medical Research Project-Young and Middle-aged High-level Talent Project (2020GDRC011), and Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing (20190112), Chongqing General Hospital Medical Science and Technology Innovation Project (2019ZDXM08)."