A peroxidase-mimetic platinum nanocluster induces concurrent DNA damage and oxidative cleavage in paediatric glioblastoma cells

Abstract

The impermeability of the blood–brain barrier (BBB), formed by a monolayer of endothelial cells, remains a major obstacle for delivering chemotherapeutic drugs to the brain. Ultra-small nanoparticles, particularly nanoclusters smaller than 2 nm, offer a promising strategy to overcome this challenge. Here, we investigate the anti-cancer efficacy and underlying mechanisms of two sizes of platinum-based nanoparticles; platinum nanoclusters (PtNCs: 2 nm) and platinum nanoparticles (PtNPs: 10 nm), synthesized using bovine serum albumin (BSA) as a stabilizer. In this study, PtNCs and PtNPs were tested against paediatric glioblastoma (p-GBM) cells, and were shown to induce cell death, prevent cell migration, and cause cell reproductive death. The mechanism of action of the PtNCs and PtNPs was investigated and compared with cisplatin by examining oxidative stress status, DNA damage, cell cycle arrest, and cell apoptosis. PtNCs exhibited promising catalytic ability under acidic conditions and physiological temperature. They showed the ability to generate free radicals to induce oxidative stress in p-GBM cells, thus causing DNA double strand breaks and G2/M phase cell cycle arrest. Conversely, PtNPs induced S phase cell cycle arrest by causing DNA crosslinking. These findings demonstrate that the cell death mechanism of Pt-based nanoparticles is critically size-dependent. This construct therefore has the potential for an improved anti-cancer treatment for paediatric glioblastoma with negligible cytotoxicity towards the normal organs. It is suggested that PtNCs could provide a promising treatment for p-GBM, and an alternative to conventional platinum-based drugs.