Pt(<sc>iv</sc>) prodrug as a potent nanosonosensitizer self-cyclically amplifies sonodynamic-chemotherapy with dually reversing cisplatin resistance

被引：0

作者：

Li, Wenxin ^{[1
]}

Lin, Ziyi ^{[1
]}

Liu, Jiahui ^{[1
]}

Zhang, Jiarui ^{[1
]}

Li, Yuxuan ^{[1
]}

Liu, Yian ^{[1
]}

Yuan, Xinru ^{[1
]}

Li, Huimin ^{[1
]}

Shen, Heyun ^{[1
]}

机构：

[1] Beijing Univ Chem Technol, Beijing Key Lab Bioproc, Beijing 100029, Peoples R China

来源：

JOURNAL OF MATERIALS CHEMISTRY B | 2025年 / 13卷 / 09期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

NANOPARTICLE; DELIVERY;

D O I：

10.1039/d4tb02615b

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

Although sonodynamic therapy (SDT) has shown promising advancements in combination with chemotherapy, it frequently necessitates the requirement of conventional sonosensitizers and chemotherapeutic agents, engendering intricate systems and potential drug resistance. Herein, we fabricated a potent Pt(iv)-poly(amino acid) coordination nanosonosensitizer (PHPt) with dual reversal of cisplatin resistance, producing abundant 1O2 and (OH)-O-center dot upon ultrasound irradiation without the use of any external sonosensitizers. The Pt(iv) prodrug in PHPt efficiently reduced to cisplatin through SDT-induced H-center dot and glutathione (GSH), inducing (OH)-O-center dot accumulation and CDDP release, which further amplified the oxidative stress on SDT. Moreover, the high GSH depletion performance of PHPt and administration of aspirin effectively inhibited cisplatin detoxification and activation of the nuclear factor-kappa B pathway, respectively. This cooperative action between the Pt(iv) prodrug and SDT in the tumor microenvironment promoted self-cyclic amplification of sonodynamic-chemotherapy, achieving a significant tumor inhibition rate of 99.4%. Thus, this study offers novel perspectives on the sonosensitizer development and cisplatin application in SDT.

引用

页码：3186 / 3197

页数：12