Dual-targeted nanoformulation with Janus structure for synergistic enhancement of sonodynamic therapy and chemotherapy  

作　　者：Zhifang Wang Man Wang Yanrong Qian Yulin Xie Qianqian Sun Minghong Gao Chunxia Li 

机构地区：[1]Institute of Molecular Sciences and Engineering,Institute of Frontier and Interdisciplinary Science,Shandong University,Qingdao 266237,China

出　　处：《Chinese Chemical Letters》2023年第7期454-460,共7页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (Nos. 52250077, 52272156, 51872263 and 52202175);Taishan Scholars Project (No. ts20190911);Shandong Natural Science Foundation (No. ZR2020ZD36);Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515010461)。

摘　　要：The accurate delivery of nanoparticles and organic small molecule drugs remains a serious challenge in nanoparticle-based tumor therapy.Dual-targeted therapy combining tumor cell targeting and organelle targeting is an effective solution.Here,an anticancer nanoformulation accurate delivery system was prepared using hyaluronic acid (HA) targeting CD44 receptors on the surface of tumor cells and IR780iodine (IR780) targeting mitochondrial for delivery.The system is based on an ultra-small Janus structured inorganic sensitizer TiO_(2-x)@NaGdF_(4) nanoparticles (TN NPs) prepared by one-step pyrolysis,further loaded with organic small molecule acoustic sensitizer IR780 and mitochondrial hexokinase Ⅱ inhibitor lonidamine (LND),followed by encapsulation of HA.Ultra-small size nanoparticles exhibit strong tissue penetration,tumor inhibition and in vivo metabolism.Under ultrasound radiation,TN NPs and IR780could produce a synergistic effect,effectively increased the efficiency of reactive oxygen species (ROS)production.Meanwhile,the released IR780 could smoothly target the mitochondria,and the ROS produced by IR780 can destroy the mitochondrial structure and disrupt the mitochondrial respiration.LND could inhibit the energy metabolism of tumor cells by reducing the activity of hexokinase Ⅱ (HK Ⅱ),which further accelerates the process of apoptosis.Furthermore,since the Janus structure allows the integration of multifunctional components into a single system,TN NPs can not only serve as an acoustic sensitizer to generate ROS,but the Gd element contained can also act as the nuclear magnetic resonance (MR)imaging contrast agent,suggesting that the nanoformulation can enable imaging-guided diagnosis and therapy.In conclusion,a new scheme to enhance sonodynamic therapy (SDT) and chemotherapy synergistically is proposed here based on ultra-small dual-targeted nanoformulation with Janus structure in the ultrasound radiation environment.

关 键 词：Ultra-small Janus structure Mitochondrial targeting CD44 targeting Synergistic therapy MR imaging 

分 类 号：R730[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]