Polymeric Micelles loaded with Indocyanine Green as Near-Infrared contrast candidates for image-guided tumor surgery

LECOT N.; FERNANDEZ LOMONACO M; MOGLIONI A.G.; CERECETTO H.; GAMBINI J.P.; CABRAL P.; GLISONI R.J.*

Caba, Buenos Aires Argentina

Congreso; III International Congress in Translational Medicine; 2016

IMBS Congress Team - FFyB, UBA.

Indocyanine green (ICG) is a FDA-approved near infrared (NIR) dye used as a contrast agent for medical diagnosis. However, it suffers from some disadvantages in clinical applications: self-aggregation in solution, poor targeting and a short half-life in vivo due to the fast uptake to the liver. To overcome these obstacles, we have utilized in this work, the amphiphilic block copolymers based on poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) to deliver ICG. PMs offer several advantages owing to their singular properties, including: (i) a good stability in water above its critical micelle concentration (CMC), (ii) high payloads, (iii) ability to modify their surfaces with a variety of receptor targeting ligands and (iv) the nano-scale sizes which is suitable for taking in advantage the enhanced permeability and retention (EPR) effect for cancer diagnosis. The EPR effect is the unique phenomenon of solid tumors related to their anatomical and pathophysiological differences from normal tissues. In addition to the EPR effect, the core-shell of PEO-PPO PMs would provide a longer half-life in circulation. As mentioned, the aim of this work was to explore the ICG encapsulation within pristine (F127 and T1307) and glucosylated (F127-Glu and T1307-Glu) PMs (10% w/v). Pristine T1307 and T1307-Glu PMs provided a complete encapsulation efficiency (EE = 100%) of ICG in aqueous solution (375µg/mL) while this was reduced to 10 and 55% for F127 and F127-Glu, respectively. The nanomicelles loaded with ICG were fully characterized for the particle sizes (two marked populations between 24-27 nm and 6-7 nm for F127 and F127-Glu, and one population of 16-21 nm for T1307 and T1307-Glu; PDI < 0.5) and Z-potentials (-6±1 mV), at 37°C by dynamic light scattering (DLS). The lyophilized ICG-loaded PMs were stable in particle size and Z-potential after these resuspended in ultrapure water. Finally, the in vivo studies reveal an enhanced circulation time and a good performance of an imaging agent in BALB/c mice with an induced 4T1 murine mammary tumor cell line, more specifically for the glucosylated poloxamine derivatives. The preliminary results indicate that ICG within PEO-PPO PMs could serve as potential non-invasive NIR contrast candidates for image-guided tumor surgery.