Construction of dual functional CuAl-LDHs nanocomposite loaded with IGF2BP3 siRNA for enhanced therapy of gastric cancer
作者全名：Li, Haiping; Zhang, Yuying; Huang, Bo; Yang, Feifei; Ma, Qiang; Wang, Xiaolin; Liu, Yuying; Ren, Junwu; Pan, Xiaojuan; Liang, Ce; Wang, Shimin; Ning, Hao; Qin, Changhong; Jiang, Yan; Ran, Ai; Xiao, Bin
作者地址：[Li, Haiping; Zhang, Yuying; Huang, Bo; Yang, Feifei; Ma, Qiang; Wang, Xiaolin; Liu, Yuying; Ren, Junwu; Pan, Xiaojuan; Liang, Ce; Wang, Shimin; Ning, Hao; Qin, Changhong; Jiang, Yan; Ran, Ai; Xiao, Bin] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Li, Haiping] Shaanxi Coal & Chem Technol Res Inst Co Ltd, Xian 710000, Peoples R China
通信作者：Xiao, B (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China.
来源：CHEMICAL ENGINEERING JOURNAL
ESI学科分类：ENGINEERING
WOS号：WOS:001208761300001
JCR分区：Q1
影响因子：13.3
年份：2024
卷号：485
期号：
开始页：
结束页：
文献类型：Article
关键词：LDHs; Fenton -like reaction; si-IGF2BP3; Gastric cancer
摘要：Gastric cancer (GC) is a prevalent malignancy in China, necessitating innovative treatments. Recent advancements in nucleic acid drugs, particularly small interfering RNAs (siRNAs), have shown promise in therapeutic applications. Biodegradable layered double hydroxides (LDHs), as a class of typical two-dimensional (2D) materials, hold great prospects in biomedical and drug delivery systems. Building on our previous research, which identified the upregulated insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) promoted GC progression, we devised a strategy that leverages the unique properties of LDHs carriers with siRNA therapeutics. Herein, we synthesized CuAl-LDHs containing variable valence metal cations (Cu2+), capable of inducing a Fenton-like reaction in the tumor micro-acid environment (TME) of GC. Subsequently, we constructed siIGF2BP3/CuAl-LDHs nanocomposites to protect and deliver si-IGF2BP3 via the CuAl-LDHs carrier. The obtained nanocomposites demonstrated significant efficacy in inhibiting GC cell proliferation by silencing the IGF2BP3 gene at both the mRNA and protein levels, accelerating oxidative stress in GC cells through a Fentonlike reaction, and achieving greater suppression of tumor volume than CuAl-LDHs alone. The remarkable antitumor effect was attributed to the CuAl-LDHs carrier's superior siRNA immobilization and delivery capabilities, as well as the catalytic ability of Cu in CuAl-LDHs, facilitating the Fenton-like reaction within TME. Overall, this integrated GC therapy strategy employing LDHs nano-carriers may represent a significant advancement in developing next-generation therapeutic systems. It underscores the potential of LDHs as an effective platform for targeted GC therapy.
基金机构：National Natural Science Foundation of China [82373001, 81872392, 82073254]; Chongqing Talents-Exceptional Young Talents Project [CQYC202005044, cstc2021ycjh- bgzxm0094]; Innovation and Development Joint Foundation of Chongqing Natural Science Foundation [CSTB2022NSCQ-LZX0043]; Science and technology research project of Chongqing Municipal Education Commission [KJZD-K202100405]; Future Medical Youth Innovation Team Project of Chongqing Medical University [W0042]; Graduate Tutor Team Construction Project of Chongqing [CQMUDSTD202210]; Top Graduate Talent Cultivation Program of Chongqing Medical University [BJRC202230]; Chongqing Postdoctoral Science Foundation Project [CSTB2022NSCQ-BHX0707]
基金资助正文：This study was supported by National Natural Science Foundation of China (82373001, 81872392, 82073254) , Chongqing Talents-Exceptional Young Talents Project (CQYC202005044, cstc2021ycjh- bgzxm0094) , Innovation and Development Joint Foundation of Chongqing Natural Science Foundation (CSTB2022NSCQ-LZX0043) , Science and technology research project of Chongqing Municipal Education Commission (KJZD-K202100405) , Future Medical Youth Innovation Team Project of Chongqing Medical University (W0042) , Graduate Tutor Team Construction Project of Chongqing (CQMUDSTD202210) , Top Graduate Talent Cultivation Program of Chongqing Medical University (BJRC202230) , Chongqing Postdoctoral Science Foundation Project (CSTB2022NSCQ-BHX0707) .
