Quantitative diffuse optical spectroscopy and T1 mapping of gadolinium-incorporated porphysome nanoparticles for guided theranostics of oral cancer in mice

Porphysomes are liposomal nanoparticles composed of photoactive porphyrin-lipid conjugates that exist either in intact or dissociated states. When intact, their tight packing density quenches fluorescence while their 100 nm diameter causes preferential accumulation in tumors through the enhanced permeability and retention effect. When processed by tumor cells, porphysomes dissociate into their subunits, unquenching their fluorescence and increasing their photoactivity. Magnetic resonance imaging (MRI) contrast is enabled by including gadolinium into the porphyrin-lipid conjugates. The passive tumor targeting and multimodal contrast present opportunities for novel oncological theranostic workflows. For instance, preoperative T1-weighted MRI enables margin assessment and/or specific uptake of the agent, while intraoperative optical measurements can distinguish residual tumor or aid in photodynamic therapy planning and monitoring. Here we compare MRI tumor contrast of gadolinium porphysomes (GPs) or gadolinium J-porphysomes (JGPs) versus Gadovist, and determine if diffuse reflectance and quantitative fluorescence spectroscopic (DRS/QFS) point measurements of porphysome concentration (GPs or JGPs) enable delineation of residual tumor. These tests used an oral squamous cell carcinoma (MOC2) tongue xenograft mouse model. Five mice were injected intravenously with GPs and JGPs, then measured at 15 minutes, 24 hours, and 44 hours post injection with T1 mapping in a 7T MRI, and with the DRS/QFS probe. Frank contrast was observed between tumor and healthy tissue in both MRI and spectroscopic measurements with broad agreement of total porphysome concentration between these measures at all measured time points. GPS and GJPS had significantly longer half-lives than Gadovist, with greater tumor specific uptake.