Exploiting cellular delivery of conjugated polymer nanoparticles for improved photodynamic therapy in a 3D glioblastoma model

Photodynamic Therapy (PDT) has recently gain attention as alternative treatment of Central Nervous System (CNS) cancer diseases, due to the demonstration of successfully elimination of gliomas in patients. The implementation of PDT for brain tumors, and especially glioblastoma (GBM), has already been approved in some countries. Due to their superb light absorption and photostability conjugated polymer nanoparticles (CPNs) are promising photosensitizers (PS) for use in PDT. Recently, we developed metallated porphyrin-doped CPNs for PDT and demonstrated that they were effective eliminating glioma cells trough ROS-mediated photoinduced damage. A problem of many therapies used to eradicate brain gliomas is the difficulty of arrival and preferential accumulation of the active drug into the tumor upon systemic administration due to the selective permeability of the blood-brain barrier (BBB). To solve this problem our approach employs mononuclear cells, which can cross BBB and infiltrate tumors, as stealth carriers for drug delivery into brain tumors. In this study loading of CPNs into monocytes/macrophages was demonstrated and the cellular functionality, chemotaxis and penetration of these loaded monocytes/macrophages into GBM spheroids (3D tumor models) was tested. CPNs loading was successfully achieved using human monocytes THP-1 and mouse bone marrow-derived monocytes (BMdM) without disturbing cell viability and differentiation potential towards macrophage state. CPNs-loaded monocytes were found to better infiltrate spheroids as compared to CPNs. Furthermore, PDT efficacy on GBM spheroids was improved when using our monocyte-mediated delivery strategy