Design of Over-1000 nm Near-Infrared Fluorescent Polymeric Micellar Nanoparticles by Matching the Solubility Parameter of the Core Polymer and Dye

Abstract

Polymeric micellar nanoparticles (PNPs) encapsulating over-thousand-nanometer (OTN) near-infrared (NIR) fluorescent dye molecules in block polymers having hydrophobic and hydrophilic chains are promising agents for the dynamic imaging of deep tissue. To achieve OTN-NIR fluorescent PNPs (OTN-PNPs) having high brightness, it is crucial to increase the affinity between the core polymer and dye molecules by matching their polarities; thus, criteria and methods to evaluate the affinity are required. In this study, we used the Hansen solubility parameter (HSP), including the polarity term, to evaluate the affinity between the two substances. HSP values of the OTN-NIR fluorescent dye IR-1061 and four core polymers, poly­(lactic-co-glycolic acid) (PLGA), poly­(lactic acid) (PLA), poly­(ε-caprolactone) (PCL), and polystyrene (PSt), were calculated using the Hansen solubility sphere method and molecular group contribution method, respectively. The relative energy density between IR-1061 and each core polymer calculated using their HSP values revealed that the affinities of PLGA and PLA for IR-1061 are higher than those of PCL and PSt. Therefore, OTN-PNPs composed of PLGA, PLA, and PCL core polymers were prepared and compared. The OTN-PNPs having PLGA and PLA cores could be loaded with larger amounts of IR-1061, had higher photoluminescence intensities, and showed higher stability in phosphate buffered saline than those having PCL cores. Moreover, the OTN-PNPs having PLGA or PLA cores were used for the dynamic imaging of live mice. Thus, matching the solubility parameters of the core polymer and dye molecule is a useful approach for designing high-performance OTN-NIR fluorescent probes.

Near Infrared Fluorescent Nanostructure Design for Organic/Inorganic Hybrid System

“…For designing highly fluorescent nanoparticles encapsulating IR-1061, a quantitative evaluation of the affinity of the dye molecule and the core polymer is useful, which can be estimated using solubility parameters. Previous studies have demonstrated that matching the solubility parameters of dyes and core polymers realizes the design of high-performance fluorescent polymeric micellar nanoparticles containing hydrophobic dyes [ 57 ], as shown in Figure 2 a. The Hansen solubility parameter (HSP) is described by three components—dispersion, polarity, and hydrogen bonding separately [ 58 , 59 ] (see Section 3 for details)—and thus allows quantitative consideration of the polarity of molecules.…”

“…The HSPs of dye molecules, even if they are an ionic compound such as IR-1061, can be calculated by the Hansen solubility sphere method [ 65 ] from the results of solubility tests in various organic solvents. When a micellar nanoparticle is composed of a polymer core having a chemical structure with a small energy difference from the dye molecule IR-1061, based on the three factors of dispersion, polarity, and hydrogen bonding, the nanoparticle encapsulates the dye with high efficiency and provides a probe with high fluorescence performance and encapsulation stability [ 57 ]. Note that the increased affinity between the dye and the polymer prevents the invasion of water molecules that can couple with IR-1061 as a quencher into the hydrophobic core of polymer micelles.…”

“…The polarity term mostly contributes to the affinity between the polymers and the dye. As shown in Figure 2 b, stable fluorescent nanoparticles containing IR-1061 show long circulation (several hours) in the blood and provide contrasts on cancer lesions [ 57 ], possibly via the enhanced permeability and retention effect [ 66 ]. Modification of the core structure of PEG- block -PCL micellar nanoparticles also altered their stability in an in-vivo environment.…”

“…( c ) Schematics of NIR fluorescent dye-loaded polystyrene (PSt) nanoparticles. ( a , b ) are adapted from reference [ 57 ] and ( c ) from reference [ 28 ] with permission with the terms of the Creative Commons CC BY license.…”

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

“…Poly(lactic acid) (PLA), a well-known biocompatible and biodegradable polymer that is widely used to make fluorescent probes and drug delivery carriers in biomedical research, 40–44 is well-suited for IR-1061 encapsulation based on its solubility parameter. 32 Since lactic acid exists in two optical isomeric forms, l -lactate and d -lactate, there are different types of PLA: poly( dl -lactic acid), a d - and l -lactic acid copolymer (PDLLA); poly( l -lactic acid) (PLLA); and poly( d -lactic acid) (PDLA). While only PDLLA was used in our previous study, 32 it has a different crystallinity from enantiomerically homogenous PLLA and PDLA 45 and may show different imaging results of tumors as suggested when loaded with indocyanine green.…”