Abstract

Silk was easily dyed in traditional textile industry because of its strong affinity to many colorants. Herein, the biocompatible silk fibroin was firstly extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano-platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily encapsulated into SFNPs with a very high encapsulation efficiency reaching to 97.7 ± 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle size of 209.4 ± 1.4 nm and a negative zeta potential of −31.9 mV, exhibiting a good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release profile of ICG in vitro, and only 24.51 ± 2.27% of the encapsulated ICG was released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal effect than free ICG after exposure to near-infrared irradiation. The temperature of ICG-SFNPs rapidly increased by 33.9 °C within 10 min and maintained for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in vitro, and a strong red fluorescence of ICG was observed in cytoplasm for cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through vein injection. Moreover, the temperature of tumor site was rapidly rising up to kill tumor cells after local NIR irradiation. After treatment, its growth was completely suppressed with the relative tumor volume of 0.55 ± 033 while free ICG of 33.72 ± 1.90. Overall, ICG-SFNPs may be an effective therapeutic means for intraoperative phototherapy and imaging.

Highlights

  • Glioblastoma, especially Glioblastoma multiforme (GBM), is far from defected by mankind

  • These results suggested that the encapsulation of indocyanine green (ICG) in silk fibroin (SF) nanoparticles (SFNPs) might prevent its interaction with the surrounding environment and delay its decomposition improving the photothermal effect of ICG (Sheng et al, 2014)

  • The encapsulated ICG was slowly released from SFNPs without any platform and the cumulative release percentage was only 24.51 ± 2.27% of the encapsulated ICG within 72 h. These results suggested a good stability of the encapsulated ICG in SFNPs and strong affinity between ICG and SFNPs to retain ICG (Salis et al, 2015)

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Summary

Introduction

Glioblastoma, especially Glioblastoma multiforme (GBM), is far from defected by mankind. SF has been used in a variety of biomedical applications and in different formats; it has been widely employed as medical sutures, for bone and cartilage tissue engineering or recently in clinical trials for the reconstruction of the tympanic membrane and breast implants This biomaterial has broadly been used in local application in clinical or preclinical modes, few of them has been reported for intravenous application (Mottaghitalab et al, 2015). A representative fluorescent dyes rhodamine B was used to feed silkworms and form dimers in body, which was absorbed into SF in vivo to trace xenobiotics in silkworm’s gland These interesting phenomenon indicated a close interaction between the SF and certain natural dyes (Tansil et al, 2011). The stiffening of tumor after treatment was detected by ultrasound shear wave elastography (SWE)

Materials
Extraction of SF solution
Characterization of SFNPs and ICG-SFNPs
Spectral properties of ICG-SFNPs
The photo-thermal effect of ICG-SFNPs
In vitro release of ICG-SFNPs
In vitro cell experiments
In vivo study of the ICG-SFNPs
2.10. In vivo imaging and tumor accumulation effect
Results and discussions
Spectral properties and photo-thermal effect of ICG-SFNPs in vitro
In vitro drug release
In vitro cell uptake and cytotoxicity of ICG-SFNPs
In vivo distribution of ICG-SFNPs by in vivo imaging
In vivo inhibition of tumor growth
The systemic toxicity of ICG-SFNPs
Conclusions
Full Text
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