文献类型： 外文期刊

作者： Lin, Sheng ¹ ; Zhang, Liuwei ² ; Cui, Hongyan ² ; Wang, Yue ³ ; Zheng, Yang ⁵ ; Hu, Jianhua ¹ ; Li, Mingzhu ⁵ ; Wang, Wentao ³ ; Zhang, Shijia ⁸ ; Zhou, Kehui ⁸ ; Chen, Qixian ² ; Lan, Xiabin ⁸ ; Zhao, Yan ³ ;

作者机构： 1.Fudan Univ, Dept Macromol Sci, State Key Lab Mol Engn Polymers, Shanghai 200433, Peoples R China

2.Zhejiang Univ, Innovat Ctr Yangtze River Delta, Jiaxing 314100, Peoples R China

3.Dalian Univ Technol, Dept Gastr Surg, Canc Hosp, 44 Xiaoheyan Rd, Shenyang 110042, Liaoning, Peoples R China

4.China Med Univ, Canc Hosp, Dept Gastr Surg, 44 Xiaoheyan Rd, Shenyang 110042, Liaoning, Peoples R China

5.Liaoning Canc Hosp & Inst, Prov Key Lab Interdisciplinary Med Engn Gastrointe, 44 Xiaoheyan Rd, Shenyang 110042, Peoples R China

6.Dalian Univ Technol, Canc Hosp, Liaoning Canc Hosp & Inst, Dept Cent Lab, Shenyang 110042, Liaoning, Peoples R China

7.China Med Univ, Canc Hosp,Canc Hosp Dalian Univ Technol, Liaoning Canc Hosp & Inst, Dept Integrated Tradit Chinese & Western Med Med O, Shenyang 110042, Peoples R China

8.Zhejiang Canc Hosp, Dept Thyroid Surg, Hangzhou 310022, Zhejiang, Peoples R China

9.Wenzhou Med Univ, Zhejiang Canc Hosp, Postgrad Training Base Alliance, Hangzhou 310022, Zhejiang, Peoples R China

10.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen 518120, Peoples R China

关键词： Solid tumor; Nanomedicine; Targeted drug delivery; Prodrug nanomedicine; Tumor microenvironment-responsive; Synergistic anticancer therapy

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：12.6； 五年影响因子：12.3 ）

ISSN：

年卷期： 2025 年 23 卷 1 期

页码：

收录情况： SCI

摘要： The development of anti-tumor nanomedicines grapples with the critical challenge of achieving sustained retention and massive intratumoral distributions of chemotherapeutics. Herein, we attempted multifaceted prodrug nanomedicine with precise spatiotemporal responsiveness, integrating dual prodrugs-redox-responsive SN38 and pH-responsive thrombin and ensuring drug release coinciding with the striking tumor acidity and reductive stress, while its spatial selectivity is directed by the overexpression of integrins on cancerous cells. Most importantly, the thrombin component induces vascular occlusion within tumors, leading to normalization of the elevated interstitial fluid pressure and promoting accumulation of chemotherapeutic agents. This approach not only facilitates the massive intratumoral distribution of the nanomedicine but also ensures sustained retention of SN38 within the tumor microenvironment, thereby augmenting the cytotoxic potencies. Of note, the advanced mass spectrum mapping technology unprecedentedly validated the successful activation of the SN38 prodrug and massive distribution throughout the solid tumors for thrombin-containing nanomedicine, in stark to apparent entrapment in tumor vasculature and stroma for the conventional thrombin-free nanomedicine. Hence, the multifunctionalities of our proposed dual prodrug nanomedicine is underscored by its ability to actively target cancerous cells, induce vasculature occlusion, and orchestrate a controlled release of chemotherapeutic agents.