Trojan Horse Monocyte-Mediated Delivery of Conjugated Polymer Nanoparticles for Improved Photodynamic Therapy of Glioblastoma
Luis Exequiel Ibarra, Lucía Beaugé, Nuria Arias‐Ramos, Viviana A. Rivarola, Carlos A. Chesta, Pilar López‐Larrubia, Rodrigo E. Palacios
Abstract
Aim: To assess monocyte-based delivery of conjugated polymer nanoparticles (CPNs) for improved photodynamic therapy (PDT) in glioblastoma (GBM). Materials & methods: Human monocyte cells (THP-1) and murine monocytes isolated from bone marrow (mBMDMs) were employed as stealth CPN carriers to penetrate into GBM spheroids and an orthotopic model of the tumor. The success of PDT, using this cell-mediated targeting strategy, was determined by its effect on the spheroids. Results: CPNs did not affect monocyte viability in the absence of light and did not show nonspecific release after cell loading. Activated monocytes incorporated CPNs in a higher proportion than monocytes in their naive state, without a loss of cellular functionality. In vitro PDT efficacy using cell-mediated delivery was superior to that using non vehiculized CPNs. Conclusion: CPN-loaded monocytes could efficiently deliver CPNs into GBM spheroids and the orthotopic model. Improved PDT in spheroids was confirmed using this delivery strategy.