Abstract
In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). The resultant xenografts were imaged in vivo non-invasively with combined fluorescence scanning laser ophthalmoscopy (SLO) and volumetric optical coherence tomography (OCT) for a period up to several months. Most xenografts exhibited a latent phase followed by a stable or rapidly increasing volume, but about 1/3 underwent spontaneous remission. After prescribed growth, a population of tumors was treated with intravenously delivered doxorubicin-containing porphyrin and cholic acid-based nanoparticles ("nanodox"). Fluorescence resonance energy transfer (FRET) emission (doxorubicin → porphyrin) was used to localize nanodox in the xenografts, and 690 nm light exposure to activate it. Such photo-nanotherapy was highly effective in reducing tumor volume. Histopathology and flow cytometry revealed CD4 + and CD8 + immune cell infiltration of xenografts. Overall, the ocular model shows potential for examining the relationships between neoplastic growth, neovascularization and other features of the immune microenvironment, and for evaluating treatment response longitudinally in vivo.
Highlights
Animal models are indispensable for understanding tumor biology and for drug development
3.1 Simultaneous volumetric and fluorescence imaging of ocular xenografts Xenografts were created by subretinal microinjection of freshly passed Green fluorescent protein (GFP)+ human glioblastoma cells (U87MG-GFP) into mouse eyes (Fig. 1(A))
Eyes were imaged in vivo prior to the injection and periodically thereafter with simultaneous optical coherence tomography and confocal scanning laser ophthalmoscopy, enabling multiple features of the xenografts to be visualized and colocalized
Summary
Animal models are indispensable for understanding tumor biology and for drug development. The dorsal skin fold chamber (DSFC) model was developed over 70 years ago to facilitate optical study of implantable tumors and their microvasculature [4]. Alternatives include surgically implanted windows that allow intravital microscopy of cranium, brain, mammary gland, spinal cord, and abdominal organs [5,6,7,8,9]. While each of these models has advantages, they share the limitation that the optical window is invasive and potentially disruptive of the natural microenvironment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
