Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

Abstract

Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.

In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles

“…At 10 h, the majority of the signal in the liver disappeared possibly due to recirculation and clearance. Similar clearance patterns have been reported by other groups as well [18, 19]. Bahmani et al, recently reported that after i.v.…”

“…Bahmani et al, recently reported that after i.v. injection of free ICG in healthy mice, the signal was detectable in the liver as early as 3 minutes post-injection, reaching a peak level between 5 and 10 min, indicative of a rapid hepatic clearance from the systemic circulation, while the fluorescence signal in the liver was found to increase up to 60 min time point after NP administration [18]. Zheng et al, underlined that the relatively short circulation time of the free ICG in vivo could be attributed to fluorescence quenching of free ICG in physiological environments [19].…”

Development of Surface-Variable Polymeric Nanoparticles for Drug Delivery to Tumors

“…In mice receiving ICG-loaded NP, the fluorescence signal appeared in the gastrointestinal tract, following the typical distribution of free ICG. 33 Therefore, we chose DiR as a fluorescence label of particles for in vivo imaging. We compared NPpT and NPpT-CA to evaluate the effect of surface modification on tumor accumulation of the particles, because they showed consistently smaller particle sizes than NL counterparts (Table 1) and the size difference – another significant factor that can affect biodistribution – was much smaller (177.0 nm vs. 179.5 nm) than that of NLpT and NLpT-CA (411.3 nm vs. 270.3 nm).…”

Multimodal Magnetic Resonance and Near-Infrared-Fluorescent Imaging of Intraperitoneal Ovarian Cancer Using a Dual-Mode-Dual-Gadolinium Liposomal Contrast Agent

“…Incorporation of ICG enabled optical imaging, which has numerous advantages such as high sensitivity and spatial resolution, real-time high frame rate imaging, relatively low cost, portability, and lack of ionizing radiation exposure20. ICG fluoresces in the near infrared wavelengths, where there is negligible autofluorescence as well as limited scatter and absorption in the body.…”

“…Free ICG has a short plasma half-life (~2–4 minutes)1819. Encapsulation increases circulation time and delays maximal hepatic accumulation (>1 hour)20. Encapsulation can also increase in vivo stability, and signal intensity21.…”