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 Significance

In 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.

中文翻译：

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自稳定的丝丝胶为基础的纳米粒子：体内生物相容性和降低的阿霉素诱导的毒性。

多种胶体稳定剂和冷冻保护剂赋予了改进的纳米颗粒（NP）胶体稳定性和可再分散性。但是，低的肿瘤靶向性，递送功效和可能的副作用限制了NPs在血管递送中的应用。在这里，我们不仅介绍水溶性丝胶蛋白（SS）作为制备NP的材料，而且还介绍了分散稳定剂和防冻剂。在没有任何稳定剂的情况下，基于SS的NP（SSC @ NPs）可以抵抗血清蛋白的吸附，从而防止形成颗粒团聚体。在不添加冷冻保护剂的情况下冷冻干燥后，SSC @ NPs粉末可以很容易地重悬到NP分散液中，几乎呈单分散分布。此外，在缓慢注射的情况下，以400 mg / kg的剂量SSC @ NPs不会对小鼠产生急性毒性。此外，装载阿霉素（DOX）的SSC @ NP（DOX-SSC @ NPs）会减少DOX在心脏中的生物分布，从而减轻DOX诱导的小鼠心脏毒性，而不会影响治疗效果。我们的结果表明，当缺乏保护剂时，自稳定的SSC @ NPs可能是静脉内给药的安全有效的药物载体。

重要声明

在这项工作中，我们证明了在没有分散稳定剂的情况下，基于水溶性丝胶蛋白（SS）的NP（SSC @ NPs）可以在生物介质中保持稳定，并且冷冻干燥后的SSC @ NPs粉没有任何冷冻保护剂可以容易重新分散到NP悬浮液中。这项研究代表了第一项研究，表明水溶性SS由于其亲水性而既可以充当分散稳定剂又可以充当防冻剂。同时，这些源于SS的优点也使另一种包含SS的NP具有自我稳定性。因此，有望将SS普遍用作其他NP的表面改性材料或块状材料，以在生物介质中保持胶体稳定性。