LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer

作者全名：Liu, Ying; Tang, Rui; Cao, Yuting; Wu, Nianhong; Qin, Qiaoxi; Chen, Yuanyuan; Wei, Xi; Ren, Jianli; Sun, Yang; Zhou, Hong; Zhou, Yang; Li, Pan

作者地址：[Liu, Ying; Tang, Rui; Cao, Yuting; Wu, Nianhong; Ren, Jianli; Sun, Yang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Dept Ultrasound, Chongqing, Peoples R China; [Li, Pan] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, State Key Lab Ultrasound Med & Engn, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Liu, Ying; Qin, Qiaoxi; Zhou, Hong; Zhou, Yang] Southwest Jiaotong Univ, Peoples Hosp Chengdu City 3, Affiliated Hosp, Dept Ultrasound, 82 Qinglong St, Chengdu 610031, Sichuan, Peoples R China; [Chen, Yuanyuan] Southwest Jiaotong Univ, Peoples Hosp Chengdu City 3, Affiliated Hosp, Dept Pathol, Chengdu, Peoples R China; [Wei, Xi] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Dept Diagnost & Therapeut Ultrasonog,Key Lab Canc, Tianjin, Peoples R China

通信作者：Li, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, State Key Lab Ultrasound Med & Engn, 76 Linjiang Rd, Chongqing 400010, Peoples R China.; Zhou, Y (通讯作者)，Southwest Jiaotong Univ, Peoples Hosp Chengdu City 3, Affiliated Hosp, Dept Ultrasound, 82 Qinglong St, Chengdu 610031, Sichuan, Peoples R China.

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001209742100001

JCR分区：Q1

影响因子：10.6

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Vasculogenic mimicry; Matrix metalloproteinase-2; Low-intensity focused ultrasound; Disulfiram; Drug penetration

摘要：Background Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment.Results Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis.Conclusions Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings.

基金机构：National Natural Science Foundation Project; Chongqing Natural Science Foundation Project [cstc2021jcyj-msxmX0220]; Sichuan Natural Science Foundation Project [24NSFSC2523, 24QYCX0480]; Chengdu Science and Technology Bureau Technology Innovation Research and Development Project [2022-YF05-01492-SN]; Science and Technology Project of the Sichuan Provincial Health Commission [23LCYJ039]; Third People's Hospital of Chengdu Scientific Research Project [2023PI03, CSY-YN-01-2023-004]; [82272025]; [81971636]; [82171946]

基金资助正文：This research was funded by the National Natural Science Foundation Project (82272025, 81971636, and 82171946), the Chongqing Natural Science Foundation Project (cstc2021jcyj-msxmX0220), the Sichuan Natural Science Foundation Project (24NSFSC2523 and 24QYCX0480), the Chengdu Science and Technology Bureau Technology Innovation Research and Development Project (2022-YF05-01492-SN), the Science and Technology Project of the Sichuan Provincial Health Commission (23LCYJ039) and The Third People's Hospital of Chengdu Scientific Research Project (2023PI03, CSY-YN-01-2023-004).