Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
J Colloid Interface Sci. 2023 Sep;645:882-894. doi: 10.1016/j.jcis.2023.05.003. Epub 2023 May 7.
Photodynamic therapy (PDT), as a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species, has been widely used for eliminating cancer cells under specific wavelength light irradiation. However, the low aqueous solubility of PSs and special tumor microenvironments (TME), such as high glutathione (GSH) and tumor hypoxia remain challenges towards PDT for hypoxic tumor treatment. To address these problems, we constructed a novel nanoenzyme for enhanced PDT-ferroptosis therapy by integrating small Pt nanoparticles (Pt NPs) and near-infrared photosensitizer CyI into iron-based metal organic frameworks (MOFs). In addition, hyaluronic acid was adhered to the surface of the nanoenzymes to enhance the targeting ability. In this design, MOFs act not only as a delivery vector for PSs, but also a ferroptosis inducer. Pt NPs stabilized by MOFs were functioned as an oxygen (O) generator by catalyzing hydrogen peroxide into O to relieve tumor hypoxia and increase singlet oxygen generation. In vitro and in vivo results demonstrated that under laser irradiation, this nanoenzyme could effectively relive the tumor hypoxia and decrease the level of GSH, resulting in enhanced PDT-ferroptosis therapy against hypoxic tumor. The proposed nanoenzymes represent an important advance in altering TME for improved clinical PDT-ferroptosis therapy, as well as their potential as effective theranostic agents for hypoxic tumors.
光动力疗法（PDT）作为一种有前途的癌症治疗策略，利用光敏剂（PS）产生活性氧，已广泛用于在特定波长光照射下消除癌细胞。然而，PS 的低水溶性和特殊的肿瘤微环境（TME），如高谷胱甘肽（GSH）和肿瘤缺氧，仍然是 PDT 治疗缺氧肿瘤的挑战。为了解决这些问题，我们构建了一种新型纳米酶，通过将小的 Pt 纳米粒子（Pt NPs）和近红外光敏剂 CyI 整合到铁基金属有机骨架（MOFs）中，用于增强 PDT-铁死亡治疗。此外，透明质酸被附着在纳米酶的表面以增强靶向能力。在该设计中，MOFs 不仅作为 PS 的递送载体，而且还作为铁死亡诱导剂。由 MOFs 稳定的 Pt NPs 通过催化过氧化氢生成 O 来发挥作用，以缓解肿瘤缺氧并增加单线态氧的产生。体外和体内结果表明，在激光照射下，这种纳米酶可以有效地缓解肿瘤缺氧并降低 GSH 水平，从而增强对缺氧肿瘤的 PDT-铁死亡治疗。所提出的纳米酶代表了改变 TME 以改善临床 PDT-铁死亡治疗的重要进展，以及它们作为缺氧肿瘤有效治疗和诊断剂的潜力。
