Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to
tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the
tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of
theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood. In this regard, comparative research is needed on the behavior of nanoparticles in large animals for developing the nanoparticles to the clinical stage. In this study, we prepared fluorophore (
indocyanine green (ICG) or cyanine 5.5 (
Cy5.5))-conjugated
glycol chitosan nanoparticles (CNPs) for comparing the
tumor-targeting efficacy in VX2
tumor-bearing mouse and rabbit models. As expected, the CNPs formed nano-sized spherical nanoparticles and were stable for 8 days under aqueous conditions. The CNPs also exhibited dose-dependent cellular uptake into VX2
tumor cells without cytotoxicity. The half-life of the near-infrared fluorescence (NIRF) signals in the blood were 3.25 h and 4.73 h when the CNPs were injected into mice and rabbits, respectively. Importantly, the CNPs showed excellent
tumor accumulation and prolonged biodistribution profiles in both the VX2
tumor-bearing mouse and rabbit models, wherein the
tumor accumulation was maximized at 48 h and 72 h, respectively. Based on the excellent
tumor accumulation of the CNPs, finally, the CNPs were used in the
image-guided surgery of the rabbit orthotopic VX2 lung
tumor model. The lung
tumor tissue was successfully removed based on the NIRF signal from the CNPs in the
tumor tissue. This study shows that CNPs can be potentially used for
tumor theragnosis in small animals and large animals.