Targeting Vascular Destruction by Sonosensitizer-Free Sonocatalytic Nanomissiles Instigates Thrombus Aggregation and Nutrition Deprivation to Starve Pancreatic Cancer

被引：6

作者：

He, Yazhi ^{[1
,2
]}

Wang, Taixia ^{[2
,3
,4
]}

Song, Yiran ^{[1
,2
]}

Fang, Chao ^{[3
,4
]}

Wang, Yang ^{[1
]}

Dong, Xiulin ^{[3
,4
]}

Wang, Yurui ^{[5
]}

Yu, Tianyu ^{[1
]}

Shi, Yang ^{[5
]}

Zhang, Fan ^{[6
]}

Zhang, Kun ^{[3
,4
]}

Wang, Feng ^{[1
]}

机构：

[1] Fudan Univ, Huadong Hosp, Shanghai Med Coll, Dept Gastroenterol, 221 Yan An Xi Rd, Shanghai 200040, Peoples R China

[2] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Med Ultrasound, 301 Yan Chang Zhong Rd, Shanghai 200072, Peoples R China

[3] Univ Elect Sci & Technol China, Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Sch Med, Dept Lab Med, 32 West Second Sect,First Ring Rd, Chengdu 610072, Sichuan, Peoples R China

[4] Univ Elect Sci & Technol China, Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Sch Med, Dept Ultrasound, 32 West Second Sect,First Ring Rd, Chengdu 610072, Sichuan, Peoples R China

[5] RWTH Aachen Univ Clin, Inst Expt Mol Imaging, Dept Polymer Therapeut, Forckenbeckstr 55, D-52074 Aachen, Germany

[6] Fudan Univ, Dept Chem, State Key Lab Mol Engn Polymers & Chem, Shanghai Key Lab Mol Catalysis & Innovat Mat, 220 Handan Rd, Shanghai 200433, Peoples R China

来源：

ADVANCED FUNCTIONAL MATERIALS | 2024年 / 34卷 / 30期

基金：

中国国家自然科学基金;

关键词：

inertial cavitation; nutrition deprivation; pancreatic cancer; sonosensitizer-free sonocatalytic nanomissiles; starvation therapy; thrombus aggregates; LOW-FREQUENCY ULTRASOUND; TUMOR; MICROBUBBLES; THERAPY;

D O I：

10.1002/adfm.202315394

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Sonosensitizers in current sonodynamic therapy (SDT) often suffer from poor delivery efficiency, phototoxicity, and disputed safety. To overcome these issues, a sonosensitizers-free sonocatalytic nanomissile is constructed, wherein PLGA nanoparticles as vehicles conjugate with L-arginine (LA) and aptamer XQ2d capable of adsorbing CO2 and targeting CD71-overexpressed pancreatic cancer, respectively. The adsorbed CO2 can respond to acidic tumor microenvironment and local ultrasound to release CO2 bubbles and enhance ultrasound-triggered inertial cavitation, which can further split H2O and activate dissolved O2 to produce center dot OH and 1O2, respectively, unlocking the sonosensitizers-free sonocatalytic ROS birth. Moreover, such CO2 bubbles-enhanced inertial cavitation also can target intratumoral vascular destruction, instigate thrombus aggregation, induce nutrition and oxygen deprivation, pose hypoxia and alter tumor metabolism, thus establishing an intratumoral vascular destruction-targeted starvation therapy. The strategy is different from previous starvation therapy in which the presence of undamaged intratumoral blood vessels compromises their outcomes. Especially, the active targeting aptamer XQ2d allows more sonosensitizer-free sonocatalytic nanomissiles to retain in pancreatic cancer, significantly magnifying the sonosensitizers-free sonocatalytic therapy and starvation therapy against subcutaneous and orthotopic pancreatic cancers. Therefore, the research provides a promising route and therapeutic platform for clinical pancreatic cancer therapy. Exogenous local ultrasound and endogenous low pH in tumor microenvironment together serve as the triggers to unlock sonosensitizers-free sonocatalytic ROS birth via activating CO2 release and enhancing inertial cavitation for directly killing pancreatic cancer cells. Beyond that, CO2 bubbles-enhanced cavitation gives birth to mechanical effects to destroy blood vessel and instigate thrombosis aggregation and nutrition deprivation, further repressing pancreatic cancer. image

引用

页数：11