Peng Yingying, Jiang Hanlin, Li Bifei, Liu Yue, Guo Bing, Gan Wei
Shenzhen Key Laboratory of Flexible Printed Electronics Technology, School of Science, Harbin Institute of Technology (Shenzhen), University Town, Shenzhen 518055, China.
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
Pharmaceutics. 2023 Aug 31;15(9):2252. doi: 10.3390/pharmaceutics15092252.
Mild photothermal therapy (PTT) shows great potential to treat cancers while avoiding unwanted damage to surrounding normal cells. However, the efficacy of mild PTT is normally moderate because of the low hyperthermia temperature and limited light penetration depth. Chemotherapy has unlimited penetration but often suffers from unsatisfactory efficacy in view of the occurrence of drug resistance, suboptimal drug delivery and release profile. As a result, the combinatory of chemotherapy and mild PTT would integrate their advantages and overcome the shortcomings. Herein, we synthesized an NIR-activatable and mild-temperature-sensitive nanoplatform () composed of temperature-sensitive liposomes (TSL), heat shock protein 90 (HSP90) inhibitor (geldanamycin) and photothermal agent (), for dual chemotherapy and mild PTT in cancer cells. constructed with donor-acceptor moieties, acts as an excellent near-infrared (NIR) photothermal agent (PTA) with a high photothermal conversion efficiency (80.75%). -containing TSLs efficiently produce a mild hyperthermia effect (42 °C) under laser irradiation (808 nm, 0.5 W cm). Importantly, the phase transformation of TSL leads to burst release of geldanamycin from and this contributes to down-regulation of the overexpression of HSP90, ensuring efficient inhibition of cancer cell growth. This research provides a dual-sensitive synergistic therapeutic strategy for cancer cell treatment.
温和光热疗法（PTT）在治疗癌症方面显示出巨大潜力，同时可避免对周围正常细胞造成不必要的损伤。然而，由于热疗温度较低且光穿透深度有限，温和PTT的疗效通常中等。化疗具有无限的穿透性，但鉴于耐药性的出现、不理想的药物递送和释放特性，其疗效往往不尽人意。因此，化疗与温和PTT的联合将整合它们的优势并克服缺点。在此，我们合成了一种由温度敏感脂质体（TSL）、热休克蛋白90（HSP90）抑制剂（格尔德霉素）和光热剂（）组成的近红外激活且温度敏感的纳米平台，用于癌细胞的双重化疗和温和PTT。由供体-受体部分构建而成，作为一种具有高光热转换效率（80.75%）的优异近红外（NIR）光热剂（PTA）。含的TSL在激光照射（808 nm，0.5 W/cm）下能有效产生温和的热疗效果（42°C）。重要的是，TSL的相变导致格尔德霉素从突发释放，这有助于下调HSP90的过表达，确保有效抑制癌细胞生长。本研究为癌细胞治疗提供了一种双敏感协同治疗策略。
