State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China; Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
Biomaterials. 2018 Sep;176:60-70. doi: 10.1016/j.biomaterials.2018.05.036. Epub 2018 May 22.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）可以诱导癌细胞凋亡，而对正常细胞没有毒性。然而，其半衰期短和各种癌细胞中野生型耐药性极大地限制了其效率。在本研究中，我们报道了一种胶束杂化纳米粒子来携带 TRAIL 配体（表示为 IPN@TRAIL），用于新型光激发 TRAIL 治疗。这些 IPN@TRAIL 通过 TRAIL 纳米载体化提高了 TRAIL 的稳定性、延长了半衰期并增强了肿瘤的积累，通过双模式成像进行监测。此外，IPN@TRAIL 纳米复合材料通过 TRAIL 纳米载体化极大地增强了对耐药癌细胞的包裹 TRAIL 治疗效率。更重要的是，当受到外部激光照射时，这些纳米复合材料不仅引发了肿瘤光热治疗（PTT），而且还上调了死亡受体（DR4 和 DR5）的表达，从而导致由共递 TRAIL 配体介导的更大的细胞凋亡。这种光/TRAIL 协同效应在携带 TRAIL 耐药 A549 肿瘤模型的小鼠中表现出了可控制的强大杀伤作用。最后，这些纳米复合材料表现出快速清除而无明显的全身毒性。所有这些特性使我们的纳米复合材料成为癌症治疗中有前途的治疗诊断平台。
