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

Yuichi Ueya,Eiji Takamoto,Kotoe Ichihashi,Hisanori Kobayashi,Masakazu Umezawa,Takashi Matsuda,Kohei Soga,Masao Kamimura,Yuka Kobayashi

doi:10.1021/acsnanoscienceau.1c00010

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.

Highlights

Dynamic live imaging in the over-thousand-nanometer (OTN)near-infrared (NIR) optical window, the so-called second biological window (NIR-II),[1] allows significantly higher spatial resolution with deeper imaging depth[2−4] and lower autofluorescence[5] than imaging in the traditional visible (400−700 nm) and first NIR window (NIR-I, 700−900 nm)
We have reported a method to design OTN-NIR fluorescentdye-loaded polymeric micellar nanoparticles (OTN-polymer nanoparticles (PNPs)) by matching the solubility parameter of the core polymers to that of hydrophobic dye, which, in this study, was IR-1061
Using the Hansen solubility parameter, HSP, as an evaluation index, we found that poly(lactic-coglycolic acid) (PLGA) and poly(lactic acid) (PLA) have higher affinity for IR-1061 than PCL and PSt do

Summary

■ INTRODUCTION

Near-infrared (NIR) optical window, the so-called second biological window (NIR-II),[1] allows significantly higher spatial resolution with deeper imaging depth[2−4] and lower autofluorescence[5] than imaging in the traditional visible (400−700 nm) and first NIR window (NIR-I, 700−900 nm). Among the various OTN-NIR fluorescent imaging probes, including rareearth-doped ceramics,[6−8] single-walled carbon nanotubes,[9−12] and quantum dots,[13−15] organic-dye-based fluorophores exhibit great potential for biomedical research and clinical use because of their high biocompatibility, designable structures, and tunable optical properties.[16−18]. Polymethine molecules such as IR-26, IR-1048, IR-1051, and IR-1061 are commercially available OTN-NIR fluorophores. 100 μL of OTNPNP dispersion in PBS (50 mg/mL) was injected into the tail vein, and the OTN-NIR fluorescence images were captured using an OTNNIR fluorescence in vivo imaging system (SAI-1000, Shimadzu, Japan)

■ RESULTS AND DISCUSSION

■ CONCLUSION

■ REFERENCES