Self-Stabilized Silk Sericin-Based Nanoparticles: In Vivo Biocompatibility and Reduced Doxorubicin-Induced Toxicity

Publication date: Available online 19 May 2018
Source:Acta Biomaterialia
Author(s): Doudou Hu, Ting Li, Zongpu Xu, Di Liu, Mingying Yang, Liangjun Zhu
A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, the discounted tumor targetability, delivery efficacy and possible side effects limit the application in the vascular delivery of NPs. Here we present the water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) could resist to the serum protein adsorption, preventing the formation of particle agglomerates. Following freeze-drying without addition of cryoprotectants, the SSC@NPs powder could be easily resuspended into NP dispersion with a nearly monodispersed distribution. Additionally, SSC@NPs do not result in acute toxicity in mice at a dose of 400 mg/kg with a slow injection. Moreover, doxorubicin (DOX)-loaded SSC@NPs (DOX-SSC@NPs) diminish the biodistribution of DOX in the heart, mitigating the DOX-induced cardiotoxicity of mice without compromising therapeutic efficacy. Our results suggest that the self-stabilized SSC@NPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents.Statement of SignificanceIn this work, we have demonstrated that water-soluble silk sericin (SS)-based NPs (SSC@NPs) could keep stable in biological media in the absence of dispersion stabilizers and that SSC@NPs powder after freeze-drying lacking any cryoprotectants can be easily redispersed to NP suspension. This study represents the first work showing water-soluble SS could both act as a dispersion stabilizer and a cryoprotectant due to its hydrophilicity. Meanwhile, these merits stemmed from SS also give self-stability to another type of NPs containing SS. Therefore, it may be promising that SS can be generally used as a surface-modified material or bulk material for other NPs to maintain colloidal stability in biological media.

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