Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, School of Life Sciences, Ningxia University, Yinchuan, 750021, P. R. China.
MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
Small. 2023 May;19(21):e2204778. doi: 10.1002/smll.202204778. Epub 2023 Feb 17.
Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT.
光敏剂 (PSs) 在肿瘤的光动力治疗 (PDT) 中起着关键作用。然而，常用的 PSs 容易发生固有荧光聚集引起的猝灭和光漂白；这一缺点严重限制了 PDT 的临床应用，需要新的光治疗剂。本文设计并构建了一种多功能治疗性纳米平台（命名为 TTCBTA NP），以实现荧光监测、溶酶体特异性靶向和图像引导 PDT。具有扭曲构象和 D-A 结构的 TTCBTA 被包裹在两亲性 Pluronic F127 中，在超纯水中形成纳米颗粒（NPs）。NPs 表现出生物相容性、高稳定性、强近红外发射和理想的活性氧 (ROSs) 产生能力。TTCBTA NPs 还表现出高效的光损伤、可忽略的暗毒性、出色的荧光跟踪和对肿瘤细胞溶酶体的高积累。此外，TTCBTA NPs 用于在异种移植的 BALB/c 裸鼠 MCF-7 肿瘤中获得具有良好分辨率的荧光图像。至关重要的是，TTCBTA NPs 通过激光照射产生丰富的 ROSs，表现出强大的肿瘤消融能力和图像引导 PDT 效果。这些结果表明，TTCBTA NP 治疗性纳米平台可能能够实现高效的近红外荧光图像引导 PDT。
