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. 2021 Feb 26;13(3):305.
doi: 10.3390/pharmaceutics13030305.

Enhanced Stability of Indocyanine Green by Encapsulation in Zein-Phosphatidylcholine Hybrid Nanoparticles for Use in the Phototherapy of Cancer

Eun-Hye Lee  1   2 , Mi-Kyung Lee  2 , Soo-Jeong Lim  1
Affiliations

Enhanced Stability of Indocyanine Green by Encapsulation in Zein-Phosphatidylcholine Hybrid Nanoparticles for Use in the Phototherapy of Cancer

Eun-Hye Lee et al. Pharmaceutics. .

Abstract

Indocyanine green (ICG) is a clinically approved near-infrared dye that has shown promise as a photosensitizer for the phototherapy of cancer. However, its chemical instability in an aqueous solution has limited its clinical application. Encapsulating ICG in liposomes, phosphatidylcholine nanoparticles (PC-NP), has shown partial effectiveness in stabilizing it. Prompted by our recent finding that the zein-phosphatidylcholine hybrid nanoparticles (Z/PC-NP) provide an advanced drug carrier compared to PC-NP, we herein investigated the potential of Z/PC-NP as an improved ICG formulation. Dynamic light scattering analysis, transmission electron microscopy, and Fourier-transform infrared spectroscopy studies showed that ICG was encapsulated in Z/PC-NP without hampering the high colloidal stability of the Z/PC-NP. During storage, the Z/PC-NP almost completely inhibited the ICG aggregation, whereas the PC-NP did so partially. The Z/PC-NP also more effectively blocked the ICG degradation compared to the PC-NP. The phototoxicity of ICG encapsulated in Z/PC-NP on cancer cells was twofold higher than that in the PC-NP. The ICG encapsulated in Z/PC-NP, but not in PC-NP, maintained its photocytotoxicity after four-day storage. These findings highlight the promising potential of Z/PC-NP as an ICG formulation that provides a higher stabilization effect than PC-NP.

Keywords: hybrid nanoparticles; indocyanine green; phosphatidylcholine; photodynamic therapy; zein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) A representative negative staining TEM image of ICG-encapsulated Z/PC-NP. Scale bar: 500 nm. (b) A FTIR spectrum of zein powder, ICG powder, physical mixture and ICG-encapsulated Z/PC-NP (ICG(+) Z/PC-NP). The Z/PC-NP was prepared from 14.8 mg of lipid (DMPC:CHOL mixture) and 7 mg of zein. The Z/PC-NP samples were freeze-dried before FTIR measurement.
Figure 2
Figure 2
The effect of the zein-to-PC ratio on the mean particle size and the zeta potential of Z/PC-NP. The closed circle symbols indicate the zeta potential and the bars indicate the mean particle size.
Figure 3
Figure 3
The effect of zein hybridization on the time-dependent formation of ICG J-aggregates. Changes in the absorbance spectrum of varying ICG formulations (0.85 mg/mL ICG concentration) were determined during incubation at room temperature. Free ICG solution was prepared in 5% D-glucose. The spectrum was obtained after sample dilution with 5% D-glucose and normalized by the 780 nm absorbance of each sample on the initial day.
Figure 4
Figure 4
The effect of zein hybridization in PC-NP on the time-dependent degradation of encapsulated ICG. ICG degradation was assessed by changes in absorbance (A) and FI (B) of ICG (0.1 mg/mL) during storage at room temperature. The value on day 0 was set at 100%. Each point represents the mean ± SD; n = 3. Significant differences between the PC-NP with or without zein hybridization are indicated by asterisks: * p < 0.05; *** p < 0.001.
Figure 5
Figure 5
The effect of zein hybridization in PC-NP on the photocytotoxicity of encapsulated ICG. Each ICG formulation was used for treatment on the day of preparation (A) or after a four-day storage at room temperature (B). PC-NP and Z/PC-NP were prepared from 21.8 mg of lipid (DMPC:CHOL mixture) and 14.8 mg of lipid and 7 mg of zein mixture, respectively. Significant differences between treatments without irradiation or with irradiation are indicated by asterisks: * p < 0.05; ** p < 0.01; *** p < 0. 001.
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