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

Abstract

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.