Abstract
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.
Highlights
Tumors have abnormal blood vessels that enable the extravasation and retention of nanoparticles, which can be utilized as a means of inducing the tumor accumulation of various nanomaterials after systemic administration [1]
chitosan nanoparticles (CNPs) were prepared by directly conjugating 5β-cholanic acid to the amine group of Glycol chitosan (GC) in the presence of ethyl-3-(3-dimethylaminopropyl) -carbodiimide hydrochloride (EDC) and NHS
For monitoring the in vitro and in vivo properties of the CNPs, Cy5.5 and indocyanine green (ICG) were covalently attached to the CNPs, respectively, to label them (Figure 1a)
Summary
Tumors have abnormal blood vessels that enable the extravasation and retention of nanoparticles, which can be utilized as a means of inducing the tumor accumulation of various nanomaterials after systemic administration [1]. The main advantages of nanoparticle-based drug delivery systems are (i) the prolonged circulation time of the drugs, (ii) improved accumulation in the tumor, (iii) enhanced cellular uptake, and (iv) reduced toxicity in healthy tissues. Hydrophobically modified GC can form self-assembled nanoparticles (CNPs), and the hydrophobic inner site can be used for the encapsulation of various theranostic agents These CNPs showed prolonged blood circulation and high tumor accumulation via the EPR effect in tumor tissue, resulting in the facilitation of the efficient delivery of anticancer agents as well as imaging agents in preclinical mouse tumor models [31]. CNPs could provide more stable and enhanced tumor-specific NIRF signals than free ICG during the image-guided surgical removal of tumor tissues in the rabbit orthotopic VX2 lung tumor model. CNPs can provide advantages for tumor-targeted imaging as well as the image-guided surgery of tumors from the mouse tumor model and rabbit tumor model
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