β‑CyclodextrinEncapsulated Platinum(II)-BasedNanoparticles: Photodynamic Therapy and Inhibition of the NF-κBSignaling Pathway in Glioblastoma

This study explores cell death through photodynamic therapy (PDT) with β-cyclodextrin-encapsulated platinum­(II)-based nanoparticles (<b>Pt-NPs</b>) and the effect on the NF-κB and stress pathways in glioblastoma. The encapsulation of the cyclometalated Pt­(II) complex <b>Pt­(LL′)</b> within β-cyclodextrin (β-CD) enhances its biocompatibility, improves cellular penetration, and boosts emission, thereby increasing the effectiveness of PDT. Both <b>Pt­(LL′)</b> and <b>Pt-NPs</b> show minimal toxicity in the dark; however, <b>Pt-NPs</b> significantly increase toxicity toward glioblastoma Kr158 cells upon irradiation at 390 nm. The PDT-induced cell death is further validated through apoptosis assays and the modulation of some key survival pathways like NF-κB/p65, DJ-1, and ERp29. This is the first report of β-cyclodextrin-encapsulated platinum­(II)-based nanoparticles designed to target glioblastoma cells through PDT, offering a promising strategy for enhancing therapeutic efficacy.