Diffusion of drug delivery nanoparticles into biogels using time-resolved microMRI

Nanoparticle-based therapeutic agents can in some cases provide selective delivery to tumors, yet this field would greatly benefit from more detailed understanding of particle transport into and within tumor tissue. To provide fundamental information for optimizing interstitial transport of polymeric nanoparticles, we have developed a quantitative approach employing real-time analysis of nanoparticle diffusion into bulk biological hydrogels using microMRI. We use two distinct imaging approaches to probe the migration of two novel "theranostic" polymeric agents (combining drug delivery and contrast agent functions) into bulk hydrogels. Theranostic agent diffusion measured using time-resolved MRI agrees well with diffusion measured for simple probe particles using fluorescence spectroscopies. Furthermore, compared with established fluorescence techniques, which are restricted by sample thickness, our approach provides a three-dimensional diffusion rate and concentration distribution of nanoparticles over macroscopic distances in biological media. These results carry implications for in vivo tracking of theranostic nanoparticles into tumor interstitium. (Figure Presented).