Cross-linked nanoparticles of silk fibroin with proanthocyanidins as a promising vehicle of indocyanine green for photo-thermal therapy of glioma

Abstract

Instability of silk fibroin nanoparticles (SFNPs) in physiologic condition hinders its application as drug delivery vehicle. Herein, indocyanine green (ICG) loaded silk fibroin nanoparticles (ICG-SFNPs) was firstly prepared and then crosslinked by proanthocyanidins to obtain the stable ICG-CSFNPs for killing the residual tumour niche under near infra-red irradiation (NIR) after surgery. The particle size and zeta potentials of ICG-CSFNPs was 120.1 nm and -40.4 mV, respectively. Moreover, ICG-CSFNPs exhibited good stability of particle size in the physiological medium. Meanwhile, the stable photothermal properties of ICG-CSFNPs were not compromised even after several cycles of NIR. Few of the ICG-CSFNPs were phagocytized by RAW264.7 macrophage in vitro, while they were easily internalized by C6 glioma cells, resulting in their significant toxicity on tumour cells after NIR. The pharmacokinetic study showed that ICG-CSFNPs had a longer blood circulation time than ICG-SFNPs, making them more distribution in glioma after intravenous administration in vivo. Meanwhile, the pharmacological study showed the more effective inhibition of tumour growth was exhibited by ICG-CSFNPs in C6 glioma-bearing mice after NIR. Overall, the cross-linked nanoparticles of silk fibroin may be a promising vehicle of ICG for photothermal therapy of glioma after surgical resection.

Graphical Abstract

Keywords:

• Glioma
• indocyanine green
• silk fibroin nanoparticles
• proanthocyanidins
• physiological stability

Additional information

Funding

This research was supported by National Natural Science Foundation of China (Grant Nos. 81772316 and 81603036), key research and development programme of Zhejiang province (Grant No. 2018C03013), Zhejiang Provincial Natural Science Foundation (Grant No. LY19H180001, LQ19H300001, LY17H180008), Zhejiang provincial programme for the cultivation of high-level innovative health talents (Y.-Z.Z.), 151 talent project of Zhejiang province and 551 talent project of Wenzhou (Y.-Z.Z.), Zhejiang Provincial Foundation for Health Department (Grant Nos. 2019322086), Wenzhou Science and Technology Bureau (Y20180183), Excellent youth talents of Wenzhou Medical University (H-L Xu).