Recent Developments in Chemo-Photodynamic Nanoplatforms for Glioblastoma Treatment

Glioblastoma multiforme (GBM) remains one of the most difficult malignant brain tumours to treat due to its infiltrative nature, cellular heterogeneity, resistance to treatment and limited drug penetration across the blood-brain barrier. The combination of photodynamic therapy (PDT) with chemotherapy within a single nanoplatform offers the possibility of integrating the photogeneration of reactive oxygen species with the cytotoxic action of chemotherapeutic agents, whilst improving their coordinated delivery to tumour cells. This review summarises the latest nanoparticle-based strategies combining PDT and chemotherapy in the treatment of GBM. The literature published between January 2025 and August 2026 was identified using the PubMed, Web of Science and Scopus databases. The systems analysed included photoreactive organic nanoaggregates, ZnO-based nanocomposites, lipid nanocarriers, dual-targeting liposomes and platforms based on covalent organic frameworks. These nanoplatforms enabled various forms of therapeutic integration, including light-triggered drug release, co-encapsulation of photosensitisers and chemotherapeutic agents, targeting of mitochondria, and targeting of glioma cells and blood-brain barrier models via ligands. The available studies have generally demonstrated increased cytotoxicity following photoactivation, and selected systems have shown synergistic effects between chemotherapy and PDT. However, the available evidence is insufficient to support the translational readiness of the currently reported chemo-PDT nanoplatforms. Three of the five systems were evaluated only in vitro, only one was investigated in an orthotopic glioma model, and several studies relied on surrogate metabolic assays or irradiation conditions of limited relevance to deep intracranial disease. The current literature should therefore be regarded primarily as proof-of-concept evidence for coordinated chemo-PDT delivery rather than as evidence of clinically applicable therapy. Progress towards clinical relevance will require platforms designed around realistic light-delivery constraints, the hypoxic GBM microenvironment, brain-relevant delivery routes and therapeutically meaningful in vivo endpoints.