BONE MARROW DERIVED MONOCYTES MEDIATE THE DELIVERY OF CONJUGATED POLYMER NANOPARTICLES IN A PLECLINICAL GLIOBLASTOMA ORTHOTOPIC MODEL

LUCIA BEAUGÉ; NURIA ARIAS RAMOS; VELZI, IGNACIO RAUL; CARLOS ALBERTO CHESTA; VIVIANA ALICIA RIVAROLA; RODRIGO EMILIANO PALACIOS; PILAR LOPEZ LARRUBIA; LUIS EXEQUIEL IBARRA

MEDICINA (BUENOS AIRES)

MEDICINA (BUENOS AIRES)

Lugar: Buenos Aires; Año: 2019 vol. 79 p. 1 - 338

0025-7680

Photodynamic therapy (PDT) has recentlygain attention as alternative treatment of glioblastoma (GBM).Due to their superb light absorption and photostability,conjugated polymer nanoparticles (CPNs) are promisingphotosensitizers in PDT. However, GBM represent a challenge tocurrent treatments due to the preferential location within CentralNervous System and the presence of the blood-brain barrier(BBB) hindering the arrival and accumulation of drugs into thetumor upon systemic administration. Trojan horse therapy, usingcells with homing capabilities for GBM, was explored to facilitatethe arrival of chemotherapeutic prodrugs; but to the best of ourknowledge there are no reports on the preparation of CNPs-loaded monocytes and its evaluation in cellular delivery. Wehypothesize that bone marrow derived monocytes (BMDMs)incorporate CPNs without affecting cell functionality and crossBBB to reach GBM, as stealth carriers. To this end, we isolatedBMDMs from C57BL/6 mice using conditioned medium (CM) withM-CSF from L929 cells. The identity of monocytes (more than 90% cells) was confirmed by double staining with anti-CD11b andanti-F4/80 after 5 days of proliferation with CM. CPNs uptake byBMDMs was assayed taking advantage of the intrinsicfluorescence of CPNs using flow cytometry. The percentage ofCPNs-loaded BMDMs increased over time (68.5 ± 1.1 % at 24 h)and the amount of CPNs per cell, measure as fluorescenceintensity (MFI), also increased over time (p<0.0001). GBMorthotopic model was developed injecting GL261 cells intoC57BL/6 mice. After 14 days, BBB disruption was confirmed bygadolinium T1-enhanced MRI. Once CPNs-loaded BMDMs (2 x 106cells, n= 6) were injected intravenously, pharmacokinetics andtumor arrival were monitored by in vivo imaging system (IVIS)up to 48 h. The MFI of CPNs increased in tumors injected withloaded BMDMs compared with those injected with saline. Takingadvantage of monocytes tropism induced by GMB cells wedemonstrated that BMDMs can effectively deliver CPNs into GBMin vivo.