Bone marrow derived monocytes mediate the delivery of conjugated polymer nanoparticles in a preclinical glioblastoma orthotopic model

BEAUGE L.; ARIAS RAMOS N.; VELZI I.; CHESTA C.; RIVAROLA VA; PALACIOS R.E.; LOPEZ LARRUBIA P; IBARRA L.E.*

Mar del Plata

Congreso; Reunión Anual de Sociedades en Biocencias; 2019

SAIC

Photodynamic Therapy (PDT) has recently gain attention as alternative treatment of glioblastoma (GBM). Due to their superb light absorption and photostability, conjugated polymer nanoparticles (CPNs) are promising photosensitizers in PDT. However, GBM represent a challenge to current treatments due to the preferential location within Central Nervous System and the presence of the blood-brain barrier(BBB) hindering the arrival and accumulation of drugs into the tumor upon systemic administration. Trojan horse therapy, using cells with homing capabilities for GBM,was explored to facilitate the arrival of chemotherapeutic prodrugs; but to the best of our knowledge there are no reports on the preparation of CNPs-loaded monocytesand its evaluation in cellular delivery. We hypothesize that bone marrow derived monocytes (BMDMs) incorporate CPNs without affecting cell functionality and cross BBB to reach GBM, as stealth carriers. To this end, we isolated BMDMs from C57BL/6 mice using conditioned medium (CM) with M-CSF from L929 cells. The identity of monocytes (more than 90 % cells) was confirmed by double staining with anti-CD11b and anti-F4/80 after 5 days of proliferation with CM. CPNs uptake by BMDMs was assayed taking advantage of the intrinsic fluorescence of CPNs usingflow cytometry. The percentage of CPNs-loaded BMDMs increased over time (68,5±1,1% at 24 h) and the amount of CPNs per cell, measure as fluorescence intensity (MFI), also increased over time (p value