Polymer nanosystems as dual-imaging theranostic agents in a glioblastoma mouse model

ARIAS-RAMOS N.; SERRANO-TORRES M.; IBARRA L.E.; GUILLEN GOMEZ M.; CAVERZAN M.D.; PALACIOS R.E.; CHESTA C.A.; LOPEZ LARRUBIA P

Barcelona

Congreso; 38th Annual Scientific Meeting European Society for Magnetic Resonance in Medicine and Biology; 2021

ESMRMB

Introduction: Glioblastoma multiforme (GBM) is considered the most lethal of the malignant primary brain tumors [1]. Infact, even after aggressive treatment, survival rates are approximately 12-15 months after diagnosis [2]. Recently,nanosystems have become promising candidates for GBM diagnosis and treatment, due to their exceptional magneticproperties, biocompatibility and blood brain barrier (BBB) penetrability [3]. In our previous investigations, metallateddoped conjugated polymer nanoparticles (CPNs) (conjugated with fluorescent polymer F8BT) were visualized in tumorsby T2 weighted (T2W) MRI [4]. In this sense, this project aims to evaluate the biodistribution of two CPNs with differenttypes of cores, Fe3O4 or NiFe2O4, in mice bearing GBM flank-tumors and control mice.Methods: In vitro validation of both CPNs was performed in a phantom study with different CPNs dilutions (Fig. 1A).Afterwards, NOD-SCID mice were injected intravenously with CPNs with a Fe3O4 or NiFe2O4 core. CPN?s biodistributionwas studied by T2W magnetic resonance imaging (MRI) pharmacodynamics (Fig. 1C & D) and T2 maps (Fig. 1B) wereobtained before and after the CPNs injection in a 7T system. An hour after injection, mice were sacrificed, organs wereresected and studied by fluorescent imaging. Additionally, mice bearing C6-GBM flank tumors were studied by T2W MRIbefore and 15 minutes after intertumoral injection Fe3O4 or NiFe2O4CPNs. Then, mice were sacrificed and flanks removedfor fluorescence studies using a IVIS Lumina II system.Results: We observed a higher CPNs uptake in the liver and a moderate accumulation in the renal cortex and the renalmedulla as seen in T2W pharmacodynamics (Fig. 1C & D). The CNPs liver accumulation seem to be higher with Fe3O4than NiFe2O4 core nanoparticles (Fig. 1C). Intratumor injection studies revealed that both CPNs can be visualized in flanktumors by T2W images, showing signal decreasing in the location where the CPNs were injected (Fig. 2A). Both CPNswere also detected in the xenograft tumors by fluorescence imaging and not observed in not injected (control) tumors(Fig. 2B).Discussion: Overall, results suggest that both CPNs are good candidates to study whether they reach and accumulatein the tumor of an orthotopic and xenograft GBM model