Albumin-based cationic nanoemulsion for Protoporphyrin IX delivery in normoxic and hypoxic conditions

Glioblastoma is one of the deadliest cancers in humans, but its treatment is limited by the difficulty drugs have in crossing the blood-brain barrier. Albumin-based nanomaterials have emerged as promising drug delivery systems for neurooncology applications, particularly for the treatment of high-grade gliomas. This study presents the development and evaluation of a human serum albumin nanoemulsion (HSANE) loaded with Protoporphyrin IX (PpIX) as a nanocarrier for high-grade gliomas. HSANE was produced using the oil-in-water spontaneous emulsification method. Nanoparticles with sizes between 200 and 300 nm exhibit excellent physicochemical properties and the ability to incorporate PpIX, as evidenced by the high fluorescence of the resulting nanoemulsion. The incorporation and cytotoxicity of PpIX-loaded HSANE were assessed in three high-grade glioma cell lines (A-172, U-87 MG, and KNS-42) under normoxic and hypoxic conditions. After 6 h incubation, PpIX was found in the nuclear and perinuclear regions across all tested cell lines, indicating strong emission and supporting its potential as a carrier for diagnostic markers. Under hypoxia, HSANE showed increased nuclear internalization. For all the glioma cell lines, no cytotoxicity was observed. These results suggested nanoformulated HSANE as a promising drug carrier and tumor marker delivery system for future applications in the treatment and diagnosis of high-grade gliomas with high fluorescence signals for the detection, localization, and diagnosis of high-grade gliomas.