A tumor microenvironment-activatable CuS@TF nanosystem with intrinsic multi-nanozyme properties for NIR-II photoacoustic imaging-guided synergistic PTT/CDT
{"title":"A tumor microenvironment-activatable CuS@TF nanosystem with intrinsic multi-nanozyme properties for NIR-II photoacoustic imaging-guided synergistic PTT/CDT","authors":"Zhixing Liang, Wenyi Wang, Yanfei Liu, Tao Yuan, Jinwei Sun, Xuliang Li, Yan-Cheng Liu, Xiaohuan Guo, Yuxuan Mo, Changchun Wen","doi":"10.1007/s00604-026-08462-0","DOIUrl":null,"url":null,"abstract":"<div><p>The efficacy of single-modal chemodynamic therapy (CDT) is often restricted by the antioxidant scavenging of overexpressed glutathione (GSH) within the tumor microenvironment (TME) and insufficient catalytic kinetics. Meanwhile, traditional photothermal therapy (PTT) also faces bottlenecks of a single therapeutic mechanism and low photothermal conversion efficiency, leading to unsatisfactory overall anti-tumor outcomes. To address these challenges, we constructed a smart-responsive, core-shell multifunctional nanotheranostic platform for near-infrared-II (NIR-II) photoacoustic (PA) imaging-guided synergistic PTT/CDT. This platform utilizes copper sulfide nanoparticles (CuS) as the photothermal core, conformally coated in situ with an Fe-tannic acid (TF) metal-phenolic network (MPN) shell (CuS@TF). In the mildly acidic TME, the TF shell dissociates to expose Fe/Cu bimetallic catalytic centers possessing excellent intrinsic peroxidase-like and catalase-like activities. Driven by the synergistic reduction of endogenous GSH and tannic acid, CuS@TF not only effectively depletes antioxidant GSH but also efficiently modulates H<sub>2</sub>O<sub>2</sub> metabolism, triggering a cascade burst of highly toxic hydroxyl radicals (·OH). Furthermore, under 1064 nm laser irradiation, the highly efficient localized hyperthermia generated by the CuS core not only directly ablates the tumor but also thermodynamically boosts the catalytic kinetics of the nanozymes, achieving profound PTT-sensitized CDT. Systematic in vitro and in vivo evaluations demonstrate that, under the precise navigation of PA imaging, CuS@TF exhibits remarkable tumor eradication efficacy (with a tumor inhibition rate of ~ 96.2%) and excellent in vivo biosafety. This work provides a novel design paradigm for the development of precise synergistic tumor theranostics based on multifunctional nanozymes.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":705,"journal":{"name":"Microchimica Acta","volume":"193 11","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microchimica Acta","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s00604-026-08462-0","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The efficacy of single-modal chemodynamic therapy (CDT) is often restricted by the antioxidant scavenging of overexpressed glutathione (GSH) within the tumor microenvironment (TME) and insufficient catalytic kinetics. Meanwhile, traditional photothermal therapy (PTT) also faces bottlenecks of a single therapeutic mechanism and low photothermal conversion efficiency, leading to unsatisfactory overall anti-tumor outcomes. To address these challenges, we constructed a smart-responsive, core-shell multifunctional nanotheranostic platform for near-infrared-II (NIR-II) photoacoustic (PA) imaging-guided synergistic PTT/CDT. This platform utilizes copper sulfide nanoparticles (CuS) as the photothermal core, conformally coated in situ with an Fe-tannic acid (TF) metal-phenolic network (MPN) shell (CuS@TF). In the mildly acidic TME, the TF shell dissociates to expose Fe/Cu bimetallic catalytic centers possessing excellent intrinsic peroxidase-like and catalase-like activities. Driven by the synergistic reduction of endogenous GSH and tannic acid, CuS@TF not only effectively depletes antioxidant GSH but also efficiently modulates H2O2 metabolism, triggering a cascade burst of highly toxic hydroxyl radicals (·OH). Furthermore, under 1064 nm laser irradiation, the highly efficient localized hyperthermia generated by the CuS core not only directly ablates the tumor but also thermodynamically boosts the catalytic kinetics of the nanozymes, achieving profound PTT-sensitized CDT. Systematic in vitro and in vivo evaluations demonstrate that, under the precise navigation of PA imaging, CuS@TF exhibits remarkable tumor eradication efficacy (with a tumor inhibition rate of ~ 96.2%) and excellent in vivo biosafety. This work provides a novel design paradigm for the development of precise synergistic tumor theranostics based on multifunctional nanozymes.
单模态化学动力学治疗（CDT）的疗效经常受到肿瘤微环境（TME）中过表达谷胱甘肽（GSH）的抗氧化清除和催化动力学不足的限制。同时，传统光热疗法也面临治疗机制单一、光热转化效率低的瓶颈，导致整体抗肿瘤效果不理想。为了解决这些挑战，我们构建了一个智能响应的核壳多功能纳米治疗平台，用于近红外- ii （NIR-II）光声（PA）成像引导的协同PTT/CDT。该平台利用硫化铜纳米颗粒（cu）作为光热核心，在原位共形涂覆铁单宁酸（TF）金属酚网络（MPN）外壳（CuS@TF）。在温和酸性的TME中，TF壳解离暴露出具有优异的内在过氧化物酶和过氧化氢酶活性的Fe/Cu双金属催化中心。在内源性GSH和单宁酸协同还原的驱动下，CuS@TF不仅有效地消耗抗氧化剂GSH，而且有效地调节H2O2代谢，引发高毒性羟基自由基（·OH）的级联爆发。此外，在1064 nm激光照射下，CuS核心产生的高效局部热疗不仅可以直接消融肿瘤，还可以从热力学上提高纳米酶的催化动力学，实现ptt致敏CDT。系统的体外和体内评价表明，在PA成像的精确导航下，CuS@TF具有显著的肿瘤根除效果（肿瘤抑制率达96.2%）和良好的体内生物安全性。这项工作为开发基于多功能纳米酶的精确协同肿瘤治疗提供了一种新的设计范式。
期刊介绍：
As a peer-reviewed journal for analytical sciences and technologies on the micro- and nanoscale, Microchimica Acta has established itself as a premier forum for truly novel approaches in chemical and biochemical analysis. Coverage includes methods and devices that provide expedient solutions to the most contemporary demands in this area. Examples are point-of-care technologies, wearable (bio)sensors, in-vivo-monitoring, micro/nanomotors and materials based on synthetic biology as well as biomedical imaging and targeting.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
