Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro, Seongbuk-gu, Seoul 02792, Korea.
Department of Materials Science and Engineering, Research Institute of Advanced Materials (RIAM), Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Molecules. 2021 Oct 2;26(19):5980. doi: 10.3390/molecules26195980.
Photothermal therapy (PTT) is one of the most promising cancer treatment methods because hyperthermal effects and immunogenic cell death via PTT are destructive to cancer. However, PTT requires photoabsorbers that absorb near-infrared (NIR) light with deeper penetration depth in the body and effectively convert light into heat. Gold nanoparticles have various unique properties which are suitable for photoabsorbers, e.g., controllable optical properties and easy surface modification. We developed gold nanodot swarms (AuNSw) by creating small gold nanoparticles (sGNPs) in the presence of hydrophobically-modified glycol chitosan. The sGNPs assembled with each other through their interaction with amine groups of glycol chitosan. AuNSw absorbed 808-nm laser and increased temperature to 55 °C. In contrast, AuNSw lost its particle structure upon exposure to thiolated molecules and did not convert NIR light into heat. In vitro studies demonstrated the photothermal effect and immunogenic cell death after PTT with AuNSW. After intratumoral injection of AuNSw with laser irradiation, tumor growth of xenograft mouse models was depressed. We found hyperthermal damage and immunogenic cell death in tumor tissues through histological and biochemical analyses. Thiol-responsive AuNSw showed feasibility for PTT, with advanced functionality in the tumor microenvironment.
光热疗法(PTT)是最有前途的癌症治疗方法之一,因为 PTT 的过热效应和免疫原性细胞死亡对癌症具有破坏性。然而,PTT 需要光吸收剂,这些光吸收剂能在体内吸收更深的近红外(NIR)光,并有效地将光转化为热。金纳米粒子具有各种独特的性质,适合作为光吸收剂,例如,可控的光学性质和易于进行表面修饰。我们通过在疏水性修饰的乙二醇壳聚糖的存在下制造小的金纳米粒子(sGNPs)来开发金纳米点群(AuNSw)。sGNPs 通过与乙二醇壳聚糖的胺基相互作用而彼此组装。AuNSw 吸收 808nm 激光并将温度升高至 55°C。相比之下,AuNSw 在暴露于巯基化分子时会失去其颗粒结构,并且不会将 NIR 光转化为热。体外研究表明,AuNSW 进行 PTT 后具有光热效应和免疫原性细胞死亡。在用激光照射后向肿瘤内注射 AuNSw 后,异种移植小鼠模型中的肿瘤生长受到抑制。我们通过组织学和生化分析发现肿瘤组织中的过热损伤和免疫原性细胞死亡。硫醇响应性 AuNSw 显示出 PTT 的可行性,具有肿瘤微环境中的先进功能。