Abstract 4226: The rodent eye as a non-invasive window for understanding cancer nanotherapeutics

Abstract

Abstract We have successfully used the mouse eye as a non-surgical window for highly efficient, optical investigation of xenograft models, using a state-of-the-art ocular imaging facility, the UC Davis “EyePod”. The EyePod employs single-cell resolution intravital confocal microscopy and optical coherence tomography, performed completely non-invasively through the natural optics of the eye (1). This technology enables repeatable in vivo imaging over days, weeks and even months, quantitative tracking of tumor development and delivery of theranostic nanoparticles, and the measurement of tumor and tumor microenvironment responses. Moreover, the retina is a highly “approachable part of the brain”, so that non-invasive study of ocular tumors provides a platform for examining such critical issues as drug delivery across the blood retinal barrier (BRB) and blood brain barrier (BBB). Clinical metastasis of solid tumor to the uvea is not uncommon. Therefore, uvea/subretinal xenograft implant, even though not orthotopic, is clinically relevant. To visualize and photo-manipulate nanoparticle delivery to intraocular xenograft, we have used our recently reported nanoporphyrin (2) as the model system. This novel multifunctional porphyrin-based micellar nanoplatform allows (i) efficient encapsulation of hydrophobic chemotherapeutic drugs or fluorescent dyes, (ii) near-infra red fluorescent (NIRF) detection of the tumor via the intrinsic fluorescence of porphyrins, (iii) photodynamic therapy (PDT) and photothermal therapy (PTT) via efficient free radical and heat generation at the tumor site, respectively. Thorough understanding of how this nanocarrier distributes within the tumor microenvironment, and how it responds to controlled optical stimulation will enable us to maximize its therapeutic potential as a nano-theranostic agent. Preliminary FRET study with doxorubicin-loaded nanoporphyrin has allowed us to visualize in vivo and in real time the release of doxorubicin at the tumor site upon illumination with 680nm laser. In addition, the EyePod has enabled us to follow the tumor response over a period of 35 days. Work is currently underway to (i) develop patient-derived xenograft (PDX) model in the eye of NSG mice, and (ii) use EyePod to study the effect of tumor targeting and brain endothelial cell targeting peptides, recently developed in our laboratory, for nanodelivery into the tumor cells and across the BRB. Citation Format: Xinlei Wang, Wenwu Xiao, Yuanpei Li, Pengfei Zhang, Mayank Goswami, Robert J. Zawadzki, Edward N. Pugh, Kit S. Lam. The rodent eye as a non-invasive window for understanding cancer nanotherapeutics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4226.