Department of Hepatobiliary Surgery, The First Affiliated Hospital, Division of Life Sciences and Medicine, and Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Division of Life Sciences and Medicine, and Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China.
J Colloid Interface Sci. 2022 Nov 15;626:453-465. doi: 10.1016/j.jcis.2022.06.134. Epub 2022 Jun 30.
For photothermal therapy (PTT), the improved targeting can decrease the dosage and promote the therapeutic function of photothermal agents, which would effectively improve the antitumor effect. The tumor microenvironment (TME) and cells are targets in designing intelligent and responsive theranostics. However, most of these schemes have been limited to the traditional visible and first near-infrared (NIR-I) regions, eager to expand to the second near-infrared (NIR-II) window. We designed and synthesized a polyethylene glycol conjugated and disulfide-modified macromolecule fluorophore (MPSS). MPSS could self-assemble into core-shell micelles in an aqueous solution (MPSS-NPS), while the small molecule probes were in a high aggregation arrangement inside the nanoparticle. The pronounced aggregation quenching (ACQ) effect caused them to the "sleeping" state. After entering the tumor cells, the disulfide bonds in MPSS-NPS broke in response to a high concentration of glutathione (GSH) in TME, and the molecule probes were released. The highly aggregated state was effectively alleviated, resulting in distinct absorption enhancement in the near-infrared region. Therefore, the fluorescence signal was recovered, and the photothermal performance was triggered. In vitro and in vivo studies reveal that the Nano-system is efficient for the smart NIR-II fluorescence imaging-guided PTT, even at a low dosage and density of irradiation.
对于光热疗法（PTT），改进的靶向作用可以降低剂量并促进光热剂的治疗功能，从而有效提高抗肿瘤效果。肿瘤微环境（TME）和细胞是设计智能和响应性治疗学的目标。然而，这些方案大多仅限于传统的可见和第一近红外（NIR-I）区域，渴望扩展到第二近红外（NIR-II）窗口。我们设计并合成了一种聚乙二醇共轭和二硫键修饰的大分子荧光团（MPSS）。MPSS 在水溶液中可以自组装成核壳胶束（MPSS-NPS），而小分子探针在纳米颗粒内部呈高聚集排列。明显的聚集猝灭（ACQ）效应使它们处于“休眠”状态。进入肿瘤细胞后，MPSS-NPS 中的二硫键在 TME 中高浓度谷胱甘肽（GSH）的作用下断裂，分子探针被释放。高度聚集状态得到有效缓解，导致近红外区域的吸收明显增强。因此，荧光信号得到恢复，并触发光热性能。体外和体内研究表明，该纳米系统可有效用于智能近红外 II 荧光成像引导的 PTT，即使在低剂量和低辐射密度下也是如此。
