Mouse eye as a model for non-surical investigation of cancer nano-theranostics

Abstract

Purpose : To evaluate the feasibility of using the mouse eye as a window for non-invasive, long-term, optical investigation of xenograft models, using multimodal, cellular-resolution ocular imaging. As an “approachable part of the brain”, the retina allows examination of such issues as drug delivery across the blood retinal barrier (BRB) and blood brain barrier (BBB). Since clinical metastasis of solid tumors to the uvea is not uncommon, uvea/subretinal xenograft implants, though not orthotopic, have potential clinical relevance.

Methods : Xenografts were created by injection of glioblastoma cells between the uvea and retina in eyes of young adult nude (Nu/Nu) mice. Controlled numbers (100 to 10,000) of GFP-labeled cells were microinjected in a submicroliter volume near the central retina for visualization and application of nano-theranostics. A schematic of the injection process is shown in Fig 1. Our custom-built widefield SLO/OCT provides repeatable in vivo imaging over many weeks, allowing quantitative tracking of tumor growth, the delivery of theranostic nanoparticles, and the measurement of tumor microenvironment responses. To visualize and photo-manipulate nanoparticle delivery to the xenografts, we used our recently reported novel multifunctional porphyrin-based micellar nanoplatform.

Results : The history of a representative xenograft glioblastoma is shown in Fig 2. This mouse was investigated for 2 months after glioblastoma injection. SLO and OCT data were acquired simultaneously during imaging sessions and gave complementary information about tumor growth status. The SLO fluorescence channel allows monitoring of position and relative number of GFP-labeled glioblastoma cells, while the OCT data provided tumor volume measurement. Phase-variance OCT angiography was used to map the local vasculature, including neovascularization arising from the retina and choroid

Conclusions : Combined SLO/OCT imaging can provide in vivo cellular-level information about tumor development after initial injection, about nanocarrier distribution within the tumor microenvironment, and about tumor response to controlled optical treatment. This information will enable us to maximize the potential of light-stimulated nano-theranostic agents.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Fig 1. Schematic of the injection process (A) and a resulting xenograft seen in a pair of SLO reflectance (B) and fluorescence (C) images.

 

Fig 2. The history of a representative xenograft glioblastoma.