Oral Delivery of Photoresponsive Milk-Derived Exosomes for the Local Therapy of Glioblastoma

Most orally administered drugs struggle to reach intracerebral regions due to the intestinal epithelial barrier (IEB) and blood–brain barrier (BBB). In this study, we investigate the potential of milk-derived exosomes (mExos) as a noninvasive solution to overcome both barriers, facilitating photodynamic therapy (PDT) of the glioblastoma. By leveraging the inherent properties of mExos, our goal is to ensure optimal efficacy by delivering a concentrated dose of the photosensitizer to the desired region. In this context, we developed photoresponsive mExos loaded with the photosensitizer chlorin e6 (Ce6@mExo) for glioblastoma treatment. Intriguingly, our findings reveal that Ce6@mExo effectively traverses both the IEB and the BBB following oral administration, significantly accumulating in brain tissue. This enhanced accumulation correlates with substantial tumor cell death in a glioblastoma orthotopic model upon laser irradiation. Our study underscores the promise of milk exosomes as vehicles for brain drug delivery via oral administration, enhancing patient convenience and therapeutic efficacy.