Multimodal imaging approach to track theranostic nanoparticle accumulation in glioblastoma with magnetic resonance imaging and intravital microscopy†

Abstract

Theranostic nanoparticles (NPs) have been designed for simultaneous therapeutic and diagnostic purposes, thereby enabling personalized cancer therapy and in vivo drug tracking. However, studies thus far have focused on imaging NP tumor accumulation at the macroscopic level and correlating results with ex vivo histology. Limited evidence exists on whether in vivo NP tumor contrast enhancement on magnetic resonance imaging (MRI) correlates with in vivo NP tumor accumulation at the microscopic level. To address this gap, the purpose of our study was to correlate quantitative MRI estimates of NP accumulation with in vivo NP signal quantification as measured through two-photon intravital microscopy (IVM) in an orthotopic murine glioblastoma multiforme model (GBM). To enable multimodal imaging, we designed dual-mode NPs, composed of a carbohydrate-coated magnetic core (Ferumoxytol) as an MRI contrast agent, and a conjugated fluorophore (FITC) for IVM detection. We administered these NPs with or without a conjugated vascular disrupting agent (VDA) to assess its effect on NP delivery to GBM. We correlated in vivo MRI contrast enhancement in tumors, quantified as T₂ relaxation time, with IVM fluorescence spatial decay rate. Results demonstrated a significantly lower tumor T₂ relaxation time and spatial decay rate in tumors targeted with VDA-conjugated NPs compared to unconjugated NPs. Postmortem histological analyses validated the in vivo observations. The presented multimodal imaging approach enabled a quantitative correlation between MRI contrast enhancement at the macroscopic level and NP accumulation in the tumor microenvironment. These studies lay the groundwork for the precise evaluation of the tumor targeting of theranostic NPs.