Biomimetic platinum-based nanoplatform for photoacoustic imaging-guided multimodal glioblastoma therapy.

Glioblastoma (GBM) presents a complex therapeutic challenge owing to its aggressive progression, immunosuppressive tumor microenvironment, and the restrictive nature of the blood brain barrier (BBB). To address these limitations, we developed a biomimetic nanoplatform (Pt-IEICO-4F@dOMV) via incorporating mesoporous platinum nanoparticles (Pt NPs) as a multifunctional catalytic core. These Pt NPs catalyze the Fenton reaction to enhance chemodynamic therapy while improving photothermal conversion efficiency under near-infrared (NIR) irradiation. This dual-action mechanism not only directly destroys tumor cells via photothermal ablation but also accelerates the Fenton reaction kinetics, thereby boosting reactive oxygen species generation during photodynamic and sonodynamic therapies. 2,2'-((2Z,2'Z)-((5,5'-(4,4,9,9-tetrakis(4-hexylphenyl)-4,9-dihydro-s-indaceno[1,2-b,5,6-b']dithiophene-2,7-diyl)bis(4-((2-ethylhexyl)oxy)thiophene-5,2-diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (IEICO-4F) is an effective photosensitizer and a sonosensitizer, which is characterized by an acceptor-donor-acceptor architecture that enables efficient NIR absorption and facilitates deep-tissue penetration. The detergent-treated outer membrane vesicle (dOMV) coating facilitates BBB penetration and enables specific targeting of GBM. In vivo studies revealed robust tumor accumulation, effective photoacoustic imaging-guided multimodal therapy, and excellent biosafety. The resulting Pt-IEICO-4F@dOMV nanoplatform offers an innovative approach for GBM treatment, leveraging Pt-mediated multimodal synergy to overcome complex therapeutic barriers.