Bonan Nicole F, Ledezma Debbie K, Tovar Matthew A, Balakrishnan Preethi B, Fernandes Rohan
George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.
Institute for Biomedical Sciences, George Washington University, Washington, DC 20052, USA.
Nanomaterials (Basel). 2022 Aug 1;12(15):2645. doi: 10.3390/nano12152645.
Prussian blue nanoparticles (PBNPs) are effective photothermal therapy (PTT) agents: they absorb near-infrared radiation and reemit it as heat via phonon-phonon relaxations that, in the presence of tumors, can induce thermal and immunogenic cell death. However, in the context of central nervous system (CNS) tumors, the off-target effects of PTT have the potential to result in injury to healthy CNS tissue. Motivated by this need for targeted PTT agents for CNS tumors, we present a PBNP formulation that targets fibroblast growth factor-inducible 14 (Fn14)-expressing glioblastoma cell lines. We conjugated an antibody targeting Fn14, a receptor abundantly expressed on many glioblastomas but near absent on healthy CNS tissue, to PBNPs (aFn14-PBNPs). We measured the attachment efficiency of aFn14 onto PBNPs, the size and stability of aFn14-PBNPs, and the ability of aFn14-PBNPs to induce thermal and immunogenic cell death and target and treat glioblastoma tumor cells in vitro. aFn14 remained stably conjugated to the PBNPs for at least 21 days. Further, PTT with aFn14-PBNPs induced thermal and immunogenic cell death in glioblastoma tumor cells. However, in a targeted treatment assay, PTT was only effective in killing glioblastoma tumor cells when using aFn14-PBNPs, not when using PBNPs alone. Our methodology is novel in its targeting moiety, tumor application, and combination with PTT. To the best of our knowledge, PBNPs have not been investigated as a targeted PTT agent in glioblastoma via conjugation to aFn14. Our results demonstrate a novel and effective method for delivering targeted PTT to aFn14-expressing tumor cells via aFn14 conjugation to PBNPs.
普鲁士蓝纳米颗粒（PBNPs）是有效的光热疗法（PTT）剂：它们吸收近红外辐射，并通过声子-声子弛豫将其重新发射为热量，在肿瘤存在的情况下，这种弛豫可诱导热和免疫原性细胞死亡。然而，在中枢神经系统（CNS）肿瘤的背景下，PTT的脱靶效应有可能导致健康CNS组织受损。出于对CNS肿瘤靶向PTT剂的这种需求，我们提出了一种靶向成纤维细胞生长因子诱导14（Fn14）表达的胶质母细胞瘤细胞系的PBNP制剂。我们将靶向Fn14的抗体（一种在许多胶质母细胞瘤上大量表达但在健康CNS组织上几乎不存在的受体）与PBNPs（aFn14-PBNPs）偶联。我们测量了aFn14在PBNPs上的附着效率、aFn14-PBNPs的大小和稳定性，以及aFn14-PBNPs在体外诱导热和免疫原性细胞死亡以及靶向和治疗胶质母细胞瘤肿瘤细胞的能力。aFn14与PBNPs稳定偶联至少21天。此外，用aFn14-PBNPs进行的PTT在胶质母细胞瘤肿瘤细胞中诱导了热和免疫原性细胞死亡。然而，在靶向治疗试验中，只有使用aFn14-PBNPs时PTT才有效杀死胶质母细胞瘤肿瘤细胞，单独使用PBNPs时则无效。我们的方法在其靶向部分、肿瘤应用以及与PTT的结合方面是新颖的。据我们所知，尚未通过与aFn14偶联研究PBNPs作为胶质母细胞瘤的靶向PTT剂。我们的结果证明了一种通过将aFn14与PBNPs偶联向表达Fn14的肿瘤细胞递送靶向PTT的新颖有效方法。
