A Mito-targeted, pH-sensitive type I photosensitizer for the diagnosis and therapy in bone metastasis of triple negative breast cancer by activating pyroptosis pathway

IF 10.7 1区生物学 Q1 BIOPHYSICS

Biosensors and Bioelectronics Pub Date : 2025-05-06 DOI:10.1016/j.bios.2025.117559

Ya-Xi Ye , Jian-Cheng Pan , Yu Jiang , Pei Tang , Hai-Chao Wang , Xin-Ai Shi , Xing-Tao Zhang , Hai-Liang Zhu , Xin-Hua Liu

{"title":"A Mito-targeted, pH-sensitive type I photosensitizer for the diagnosis and therapy in bone metastasis of triple negative breast cancer by activating pyroptosis pathway","authors":"Ya-Xi Ye , Jian-Cheng Pan , Yu Jiang , Pei Tang , Hai-Chao Wang , Xin-Ai Shi , Xing-Tao Zhang , Hai-Liang Zhu , Xin-Hua Liu","doi":"10.1016/j.bios.2025.117559","DOIUrl":null,"url":null,"abstract":"<div><div>Rational design of multifunctional molecules integrating diagnostic and therapeutic capabilities represents a cutting-edge yet challenging frontier in modern medicine. In this study, we present the first report on <strong>Rh-HB</strong>, a smart near-infrared (NIR) molecular probe engineered for mitochondria-targeted theranostics in triple-negative breast cancer (TNBC) bone metastasis. As a ratiometric, dual-excitation pH-sensitive fluorescent probe, <strong>Rh-HB</strong> enables real-time monitoring of mitochondrial pH fluctuations associated with early-stage metastatic progression. Moreover, <strong>Rh-HB</strong> functions as a highly efficient type I photosensitizer, generating cytotoxic reactive oxygen species (ROS) such as superoxide anion (O<sub>2</sub><sup>•-</sup>) and hydroxyl radicals (·OH) upon light irradiation within mitochondria. This localized ROS production overcomes the limitations of short diffusion distances, ensuring effective oxidative damage. Crucially, <strong>Rh-HB</strong> induces severe mitochondrial oxidative stress, triggering pyroptosis in TNBC bone metastasis models. Thus, <strong>Rh-HB</strong> serves as a proof-of-concept theranostic agent, offering a promising strategy for combating bone metastasis of TNBC.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"283 ","pages":"Article 117559"},"PeriodicalIF":10.7000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biosensors and Bioelectronics","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0956566325004336","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOPHYSICS","Score":null,"Total":0}

引用次数: 0

Abstract

Rational design of multifunctional molecules integrating diagnostic and therapeutic capabilities represents a cutting-edge yet challenging frontier in modern medicine. In this study, we present the first report on Rh-HB, a smart near-infrared (NIR) molecular probe engineered for mitochondria-targeted theranostics in triple-negative breast cancer (TNBC) bone metastasis. As a ratiometric, dual-excitation pH-sensitive fluorescent probe, Rh-HB enables real-time monitoring of mitochondrial pH fluctuations associated with early-stage metastatic progression. Moreover, Rh-HB functions as a highly efficient type I photosensitizer, generating cytotoxic reactive oxygen species (ROS) such as superoxide anion (O₂^•-) and hydroxyl radicals (·OH) upon light irradiation within mitochondria. This localized ROS production overcomes the limitations of short diffusion distances, ensuring effective oxidative damage. Crucially, Rh-HB induces severe mitochondrial oxidative stress, triggering pyroptosis in TNBC bone metastasis models. Thus, Rh-HB serves as a proof-of-concept theranostic agent, offering a promising strategy for combating bone metastasis of TNBC.

查看原文本刊更多论文

一种mitto靶向、ph敏感的I型光敏剂通过激活焦亡途径诊断和治疗三阴性乳腺癌骨转移

综合诊断和治疗能力的多功能分子的合理设计代表了现代医学的前沿但具有挑战性的前沿。在这项研究中，我们首次报道了Rh-HB，一种智能近红外（NIR）分子探针，用于线粒体靶向治疗三阴性乳腺癌（TNBC）骨转移。作为一种比例、双激发pH敏感荧光探针，Rh-HB能够实时监测与早期转移进展相关的线粒体pH波动。此外，Rh-HB作为一种高效的I型光敏剂，在线粒体内的光照射下产生细胞毒性活性氧（ROS），如超氧阴离子（O2•-）和羟基自由基（·OH）。这种局部ROS的产生克服了短扩散距离的限制，确保了有效的氧化损伤。关键是，Rh-HB诱导严重的线粒体氧化应激，在TNBC骨转移模型中引发焦亡。因此，Rh-HB作为一种概念验证的治疗药物，为对抗TNBC骨转移提供了一种有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biosensors and Bioelectronics 工程技术-电化学

CiteScore

20.80

自引率

7.10%

发文量

1006

审稿时长

29 days

期刊介绍： Biosensors & Bioelectronics, along with its open access companion journal Biosensors & Bioelectronics: X, is the leading international publication in the field of biosensors and bioelectronics. It covers research, design, development, and application of biosensors, which are analytical devices incorporating biological materials with physicochemical transducers. These devices, including sensors, DNA chips, electronic noses, and lab-on-a-chip, produce digital signals proportional to specific analytes. Examples include immunosensors and enzyme-based biosensors, applied in various fields such as medicine, environmental monitoring, and food industry. The journal also focuses on molecular and supramolecular structures for enhancing device performance.