Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants

Abstract

Stacey Markovic,1,* Jodi Belz,2,* Rajiv Kumar,3,4 Robert A Cormack,4 Srinivas Sridhar,3,4 Mark Niedre1 1Department of Electrical and Computer Engineering, 2Department of Bioengineering, 3Department of Physics, Northeastern University, Boston, MA, USA; 4Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA *These authors contributed equally to this work Abstract: Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform. Keywords: optical imaging, fluorescence, drug delivery, brachytherapy, treatment monitoring

Keywords

• near infrared
• fluorescence imaging
• nanoparticles
• diffusion
• brachytherapy spacers