Near infrared labeling of PLGA for in vivo imaging of nanoparticles

Abstract

To introduce optical imaging among methods available to follow nanoparticle biodistribution, we have evaluated the concept of covalently labeling poly(lactide-co-glycolide) (PLGA) with a near-infrared (NIR) dye to obtain stable NIR fluorescent nanoparticles. PLGA was coupled with the NIR dye (DY-700, Dyomics) by an amide bond with 38% efficiency. Incorporating 1% of this conjugate into PLGA nanoparticles stabilised by polyvinyl alcohol (PVA) leads to stable nanoparticles (NPs) without affecting their colloidal characteristics (average diameter, polydispersity and zeta potential). In addition, nanoparticles remain strongly fluorescent and display good storage stability for 4 weeks at 4 C or over one week at 37 C. Nanoparticle cytotoxicity evaluated using HUVEC, NIH/3T3 and J774.A1 cell lines was similar for unlabeled or labeled NPs. Fluorescent nanoparticles and free dye were injected intravenously into mice and their biodistribution was followed for 24 h by NIR imaging, in vivo and ex vivo. Nanoparticles were found mainly in the liver whereas the free dye was not accumulating preferentially in this organ. The DY-700 NIR conjugate incorporated into PLGA NPs shows good performance both in vitro and in vivo, thus paving the way to finely traceable PLGA nanosystems for in vivo administration.

Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages

“…These nanoparticles are spherical and monodisperse (polydispersity index below 0.15) and remain stable for 48 h in cell culture medium. In addition, these PLGA nanoparticles can undergo covalent fluorescent labeling without modifying their physicochemical properties (Reul et al, 2012). In the present study, stabilizer-free PLGA nanoparticles have been added to this panel.…”

“…All PLGA nanoparticles were fluorescently labeled, by replacing the total quantity of PLGA by a 99/1 (w/w) mixture of PLGA and a custom-made DY700-PLGA conjugate, obtained by coupling 75:25 PLGA with a NIR (Near Infra Red)-emitting fluorescent dye (DY700, Dyomics) as previously described (Reul et al, 2012). The further steps were performed similarly to unlabeled nanoparticles, protected from light.…”

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

“…132,139 In addition, PLGA is approved by the FDA and is a component of many biodegradable market products for parenteral application. 133,140 Initially, in 2004, Saxena and colleagues prepared 300410 nm PLGA nanoparticles entrapping ICG by a modified spontaneous emulsification solvent diffusion method and were able to achieve over 74 % loading of the fluorophore in the particles. 141,142 Later in 2006, they demonstrated the use of these particles for tumor diagnosis and photodynamic therapy and also determined the biodistribution of ICG loaded PLGA nanoparticles in healthy C57BL/6 mice (female,10-week old).…”

“…This system could be developed further into a finely traceable PLGA nanosystem for fluorescence imaging. 140 Apart from PLA based nanosystems, there have been particles based on other polymers such as poly(propargyl acrylate) (PA), poly(styrene-co-methacrylic acid), and poly(acrylic acid) (PAA). In 2011 Rungta and colleagues prepared sub-100 nm PA nanoparticles which had azide-terminated indocyanine green (azICG) covalently conjugated to the surface.…”

Silica passivated conjugated polymer nanoparticles for biological imaging applications

“…These dyes have some drawbacks such as unsatisfactory brightness, rapid photo bleaching and small Stokes' shifts, which cause difficulty in detecting the signal 9 . Therefore materials that are bright, have greater photo-, bio-, and environmental stability, and a large Stokes shift are now being developed for fluorescence microscopy and clinical imaging 10 .…”