Tumor-penetrating nanoplatform with ultrasound "unlocking" for cascade synergistic therapy and visual feedback under hypoxia

作者全名："Xie, Zhuoyan; Wang, Junrui; Luo, Yuanli; Qiao, Bin; Jiang, Weixi; Zhu, Leilei; Ran, Haitao; Wang, Zhigang; Zhu, Wei; Ren, Jianli; Zhou, Zhiyi"

作者地址："[Xie, Zhuoyan; Zhu, Leilei] Chongqing Gen Hosp, Dept Ultrasound, Chongqing 401147, Peoples R China; [Xie, Zhuoyan; Wang, Junrui; Luo, Yuanli; Qiao, Bin; Jiang, Weixi; Zhu, Leilei; Ran, Haitao; Wang, Zhigang; Ren, Jianli; Zhou, Zhiyi] Second Affiliated Hosp Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Wang, Junrui] Second Affiliated Hosp Chongqing Med Univ, Dept Radiol, Chongqing 400010, Peoples R China; [Zhou, Zhiyi] Chongqing Gen Hosp, Depatment Gen Practice, Chongqing 401147, Peoples R China; [Zhu, Wei] Hubei Univ Nationalities, Dept Med Coll, Enshi 445000, Hubei, Peoples R China"

通信作者："Ren, JL; Zhou, ZY (通讯作者)，Second Affiliated Hosp Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Zhou, ZY (通讯作者)，Chongqing Gen Hosp, Depatment Gen Practice, Chongqing 401147, Peoples R China.; Zhu, W (通讯作者)，Hubei Univ Nationalities, Dept Med Coll, Enshi 445000, Hubei, Peoples R China."

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000920674000002

JCR分区：Q1

影响因子：10.2

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Nanoultrasonic biomedicine; Acoustic droplet vaporization; Nanoplatform-based cascade engineering; O-2 supply; Tumor-penetrating peptide

摘要："BackgroundCombined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O-2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy.ResultsA visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named HtLyP-1(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with O-1(2) produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O-2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O-2 supply in vitro, and achieve significant tumor inhibition in vivo.ConclusionWe present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O-2 supply, which ultimately synergistically enhanced cascade therapy."

基金机构："National Natural Science Foundation of China [82171946, 81873901, 82202181]; Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission [cstc2019jcyj-zdxmX0020]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0569]; High-level Medical Reserved Personnel Training Project of Chongqing, CQMU Program for Youth Innovation in Future Medicine [W0026]; Kuanren Talents Program of the 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]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant No.82171946, 81873901, 82202181), the Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission (Grant No. cstc2019jcyj-zdxmX0020) and the Natural Science Foundation of Chongqing (Grant No. cstc2020jcyj-msxmX0569). The authors also appreciate the High-level Medical Reserved Personnel Training Project of Chongqing, CQMU Program for Youth Innovation in Future Medicine (W0026), Kuanren Talents Program of the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (KR2019G001), the 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)."