Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 South Daxuecheng Road, Chongqing 401331, P. R. China.
Department of Pharmacy, Fuwai Central China Cardiovascular Hospital & Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan, 451464, P. R. China.
J Mater Chem B. 2023 Mar 30;11(13):2937-2945. doi: 10.1039/d2tb02776c.
Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO/ICG@ZIF-8, which was capable of self-sufficient O delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO and indocyanine green (ICG) form CaO/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO reacts with water under acidic conditions to produce O so CaO/ICG@ZIF-8 has an excellent O supply capacity, which is essential for PDT. Moreover, CaO/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both and studies. Notably, the Zn and Ca generated by CaO/ICG@ZIF-8 degradation are essential elements for the body, so CaO/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.
光动力疗法（PDT）和光热疗法（PTT）是治疗癌症的有效方法。然而，肿瘤微环境（TME）具有严重缺氧和丰富的谷胱甘肽（GSH），这极大地降低了 PDT 的效果。在这项研究中，我们开发了一种氧化应激放大器 CaO/ICG@ZIF-8，它能够自我供应 O 和耗竭 GSH，以增强 PDT 和 PTT 协同治疗。我们利用 ZIF-8 作为纳米载体，当负载 CaO 和吲哚菁绿（ICG）时，形成 CaO/ICG@ZIF-8 纳米颗粒，其具有均匀的颗粒尺寸分布和约 215nm 的水合颗粒尺寸。CaO 在酸性条件下与水反应生成 O，因此 CaO/ICG@ZIF-8 具有出色的 O 供应能力，这对于 PDT 至关重要。此外，CaO/ICG@ZIF-8 还与 GSH 反应生成谷胱甘肽二硫化物（GSSH），通过防止局部活性氧物质的消耗，增强 PDT 的治疗效果。除此之外，CaO/ICG@ZIF-8 还可以产生强烈的热疗，其光热转换效率约为 44%，非常适合 PTT。由于其增强作用，CaO/ICG@ZIF-8 介导的 PTT/PDT 在 和 研究中均表现出强烈的肿瘤抑制作用。值得注意的是，CaO/ICG@ZIF-8 降解产生的 Zn 和 Ca 是身体必需的元素，因此 CaO/ICG@ZIF-8 表现出良好的安全性。总之，该研究为癌症提供了一种有前途的 PDT/PTT 协同治疗策略，并可能在未来显示出更多的医学应用。
