Liu Wenhan, Sun Can, Dai Yuhang, Wang Huaiyong, Ashrafizadeh Milad, Conde João, Yang Liyu, He Wei
Department of Thoracic Surgery, The Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, PR China.
Department of Clinical Nutrition, The Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, PR China.
Mater Today Bio. 2025 Aug 13;34:102183. doi: 10.1016/j.mtbio.2025.102183. eCollection 2025 Oct.
In addition to early diagnosis and on-time treatment, the adoption of new therapeutic strategies is of great significance for improving the clinical outcomes of patients with esophageal cancer. Although emerging therapies such as photothermal and photodynamic therapy (PDT) can precisely eliminate cancer cells and are alternative strategies to conventional treatments, hypoxia status of solid tumors have hindered their application. In recent years, nanoplatforms have been developed to address these limitations and improve the efficacy and safety of treatments. In addition, triptolide (TPL) and HIF-1α silencing may have potential value in cancer treatment by regulating oxidative stress. Inspired by these findings, we designed a cancer cell membrane-camouflaged porphyrin (photosensitizer) metal-organic framework (Zr-MOF@CM) for the co-delivery of TPL and HIF-1α small interfering RNA (siRNA) into tumor cells and tissues. The nanoparticles (TPL/siHIF-1α@Zr-MOF@CM) achieved targeted drug/gene/PDT synergistic therapy for esophageal cancer. This portable "all-in-one" drug delivery system exhibited good biocompatibility, sensitive pH-dependent drug release, and effective phagocytosis by esophageal cancer Kyse-30 cells. In addition, the nanoparticles produced large amounts of ROS and released drugs under near-infrared light (660 nm) irradiation, which significantly increased the apoptosis of esophageal cancer cells. Meanwhile, TPL and siHIF-1α released from the nanoparticles alleviated the hypoxic condition, further improving the PDT effect. In vivo experiments confirmed that TPL/siHIF-1α@Zr-MOF@CM maintained a long circulation time in tumor-bearing mice, specifically targeted the tumor site, and played a synergistic role with PDT to effectively reduce tumor growth. Importantly, TPL/siHIF-1α@Zr-MOF@CM exhibited a favorable biosafety profile in vitro and in vivo. This nanosystem is suitable for enhancing oxidative damage at tumor sites and is instructive for future design of PDT-dependent nanoplatforms.
除了早期诊断和及时治疗外，采用新的治疗策略对于改善食管癌患者的临床结局具有重要意义。尽管诸如光热疗法和光动力疗法（PDT）等新兴疗法能够精确地消除癌细胞，是传统治疗的替代策略，但实体瘤的缺氧状态阻碍了它们的应用。近年来，已开发出纳米平台来解决这些局限性并提高治疗的有效性和安全性。此外，雷公藤内酯醇（TPL）和缺氧诱导因子-1α（HIF-1α）沉默可能通过调节氧化应激在癌症治疗中具有潜在价值。受这些发现的启发，我们设计了一种癌细胞膜伪装的卟啉（光敏剂）金属有机框架（Zr-MOF@CM），用于将TPL和HIF-1α小干扰RNA（siRNA）共同递送至肿瘤细胞和组织中。纳米颗粒（TPL/siHIF-1α@Zr-MOF@CM）实现了对食管癌的靶向药物/基因/PDT协同治疗。这种便携式的“一体化”药物递送系统表现出良好的生物相容性、对pH敏感的药物释放以及被食管癌Kyse-30细胞有效吞噬。此外，纳米颗粒在近红外光（660nm）照射下产生大量活性氧并释放药物，这显著增加了食管癌细胞的凋亡。同时，从纳米颗粒中释放的TPL和siHIF-1α减轻了缺氧状况，进一步提高了PDT效果。体内实验证实，TPL/siHIF-1α@Zr-MOF@CM在荷瘤小鼠中保持较长的循环时间，特异性靶向肿瘤部位，并与PDT发挥协同作用以有效抑制肿瘤生长。重要的是，TPL/siHIF-1α@Zr-MOF@CM在体外和体内均表现出良好的生物安全性。这种纳米系统适用于增强肿瘤部位的氧化损伤，对未来基于PDT的纳米平台设计具有指导意义。
