Heat Treatment Effects for Controlling Dye Molecular States in the Hydrophobic Core of Over-1000 nm Near-Infrared (NIR-II) Fluorescent Micellar Nanoparticles

Abstract

Organic molecules that emit near-infrared (NIR) fluorescence at wavelengths above 1000 nm, also known as the second NIR (NIR-II) biological window, are expected to be applied to optical in vivo imaging of deep tissues. The study of molecular states of NIR-II dye and its optical properties are important to yield well-controlled fluorescent probes; however, no such study has been conducted yet. Among the two major absorption peaks of the NIR-II dye, IR-1061, the ratio of the shorter wavelength (900 nm) to the longer one (1060 nm) increased with an increase in the dye concentration in tetrahydrofuran, suggesting that the 900 nm peak is due to the dimer formation of IR-1061. Both absorption peaks are also observed when IR-1061 is encapsulated in the hydrophobic (stearyl) core of micellar nanoparticles (MNPs) of a phospholipid–poly­(ethylene glycol). The dimers in the MNP cores decreased via dimer dissociation by enhancing the mobility of the hydrophobic stearyl chains by heat treatment of the dye-encapsulating MNPs at 50–70 °C. The MNPs maintained the dissociated IR-1061 monomers in the core after recooling to 25 °C and showed a higher NIR-II fluorescence intensity than those before heat treatment. This concept will provide better protocols for the preparation of NIR-II fluorescent probes with well-controlled fluorescence properties.

Effect of the enantiomeric structure of hydrophobic polymers on the encapsulation properties of a second near infrared (NIR-II) fluorescent dye for in vivo deep imaging

“…IR-1061 dimers and monomers had peaks at approximately 950 and 1070 nm, respectively. 37 The results showed that IR-1061 formed less dimers in PDLLA than in PLLA ( Fig. 2 ), suggesting that IR-1061 showed higher affinity for PDLLA than PLLA.…”

“… 24,28 Previous studies have shown that the molecular state of IR-1061 varies between monomer and dimer depending on the polymer and solvent being used, as well as its concentration. 37 In short, IR-1061 is a low polarity molecule that, while it can exist as monomers in environments with high affinity even at locally high concentration, tends to form dimers that show low fluorescence intensity in non-polar and hydrophobic environments. 37 Previous studies have shown that the aggregate formation like dimers of organic dye molecules alters their optical properties such as emission intensity and wavelength.…”

“… 37 In short, IR-1061 is a low polarity molecule that, while it can exist as monomers in environments with high affinity even at locally high concentration, tends to form dimers that show low fluorescence intensity in non-polar and hydrophobic environments. 37 Previous studies have shown that the aggregate formation like dimers of organic dye molecules alters their optical properties such as emission intensity and wavelength. 37–39 It is important to clarify the influence of the polymer on the dye's molecular state to better design highly emissive fluorescent probes using IR-1061 with less dimer formation.…”

“… 37 Previous studies have shown that the aggregate formation like dimers of organic dye molecules alters their optical properties such as emission intensity and wavelength. 37–39 It is important to clarify the influence of the polymer on the dye's molecular state to better design highly emissive fluorescent probes using IR-1061 with less dimer formation.…”

Controlling Molecular Dye Encapsulation in the Hydrophobic Core of Core–Shell Nanoparticles for In Vivo Imaging

“…The structure of the micellar nanoparticles was presumed to be such that the stearoyl group, a fatty acid chain, forms a hydrophobic core, PEG forms a hydrophilic shell, and IR-1061 is encapsulated in the core. Subsequently, many OTN-NIR fluorescent micellar nanoparticles with polymethine dyes encapsulated in various hydrophobic cores, such as DSPE [57,58], other lipids [59], polycaprolactone (PCL) [60], and polystyrene (PSt) [61] have been reported (Fig. 3).…”