高级检索

基于NIR-II荧光成像引导的I型光动力疗法用于三阴性乳腺癌治疗

Type I photodynamic therapy guided by NIR-II fluorescence imaging is used for the treatment of triple-negative breast cancer

  • 摘要: 为应对光动力疗法因依赖氧而受限、组织穿透不足的问题,本研究构建了基于给体-π桥-受体(D-π-A)结构的I型聚集诱导发光特性的光敏剂DHSTPA及其纳米颗粒(DHSTPA NPs),DHSTPA NPs具有近红外吸收和近红外二区荧光发射。其在660 nm光照下可高效产生活性氧(超氧阴离子与羟基自由基)。细胞实验表明,DHSTPA NPs可被4T1细胞有效摄取并定位溶酶体,光照后通过I型机制诱导细胞死亡。体内实验显示DHSTPA NPs在肿瘤部位富集良好,光照后能显著抑制肿瘤生长并诱导坏死凋亡,且未见明显系统毒性。结果表明,DHSTPA NPs是一种具有近红外二区发射、高效I型光动力活性及良好生物安全性的潜在光敏体系。

     

    Abstract: To address the limitations of photodynamic therapy (PDT), such as its oxygen dependence and insufficient tissue penetration, this study constructed a type-I photosensitizer with aggregation-induced emission (AIE) characteristics, named DHSTPA, based on a donor-π bridge-acceptor (D-π-A) structure, as well as its corresponding nanoparticles (DHSTPA NPs). DHSTPA NPs exhibit near-infrared absorption and second near-infrared (NIR-II) window fluorescence emission. Under 660 nm laser irradiation, they can efficiently generate reactive oxygen species (ROS), including superoxide anion and hydroxyl radicals. Cellular experiments demonstrated that DHSTPA NPs could be effectively internalized by 4T1 cells and localized in lysosomes. Upon irradiation, they induced cell death primarily via a type-I photodynamic mechanism. In vivo experiments revealed that DHSTPA NPs accumulated well at the tumor site. Following light exposure, they significantly inhibited tumor growth and induced necrosis and apoptosis, with no observed significant systemic toxicity. These results indicate that DHSTPA NPs represent a promising photosensitizing system with NIR-II emission, efficient type-I photodynamic activity, and favorable biosafety.

     

/

返回文章
返回