Translational image-guided nanoneurosurgery in the surgical management of glioblastoma: Applications of porphyrins, gold nanoparticles and prospective management

Introduction Glioblastoma multiforme (GBM) is an aggressive and highly infiltrative primary brain tumor with a dismal prognosis. Tumor heterogeneity and hypoxia-driven angiogenesis shape a hostile microenvironment that limits maximal safe resection and promotes therapeutic resistance. Despite advances in multimodal management, conventional neurosurgical strategies remain insufficient. In this context, porphyrin-based agents and gold nanoparticle (AuNP) platforms have emerged as adjunctive technologies with potential to enhance intraoperative guidance and postoperative adjuvant therapies. Methods A thematic review was conducted to analyze porphyrin- and AuNP-based nanoengineered systems in GBM. Searches were performed in PubMed, Scopus, ScienceDirect, and Springer Nature for studies published between 2020 and 2025. Article screening was independently performed using Rayyan IA software. Results A total of 316 records were identified, 41 duplicates were removed, and 42 studies met inclusion criteria. Most evidence derived from preclinical models, with limited early-phase clinical data. Overall, nanoconjugates demonstrated improved biodistribution and enhanced photodynamic and photothermal effects. Discussion The GBM microenvironment characterized by hypoxia, aberrant angiogenesis, metabolic plasticity, and cancer stem cells drives surgical and adjuvant treatment failure. AuNP platforms enable synergistic PDT/PTT, support fluorescence-guided resection, and facilitate targeted delivery. Translational strategies such as optoBBTB and convection-enhanced delivery showed tumor reduction in murine models, while talaporfin-based PDT and the ongoing Phase I/II AGuIX trial suggest clinical feasibility with modest benefit. Conclusions Porphyrin–AuNP nanoplatforms represent a promising adjunct in neuro-oncological surgery. However, clinical implementation remains constrained by limited human evidence and lack of standardized protocols. Multicenter trials and workflow-oriented frameworks are required before routine neurosurgical adoption.