State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, No. 2 Tiansheng Road, Chongqing 400715, P. R. China.
Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, No. 2 Tiansheng Road, Chongqing 400715, P. R. China.
ACS Biomater Sci Eng. 2020 Feb 10;6(2):1052-1063. doi: 10.1021/acsbiomaterials.9b01676. Epub 2020 Jan 13.
Combinational cancer therapy offers a promising strategy to overcome the limitations of single-drug treatment, including limited therapeutic efficacy, serious side effects, and low survival rate. Injectable silk fibroin (SF) hydrogel has emerged as an effective platform for localized treatment. Herein, hydrophilic SF (HSF) was extracted from regenerated SF and self-assembled into hydrogel within 2-6 h. The obtained HSF hydrogel showed obvious viscoelasticity, thixotropic behavior, and self-healing performance. Interestingly, this hydrogel also exhibited excellent stimuli-responsive drug release profiles when triggered by multiple factors (acidity, reactive oxygen species, glutathione, hyperthermia, and near-infrared (NIR)), suggesting that it could achieve spatially and temporally on-demand drug release in response to tumor microenvironment and extra-tumor NIR irradiation. Importantly, intratumoral injection of doxorubicin (DOX)/Cy7-loaded HSF-based hydrogel (DOX/Cy7-hydrogel) plus NIR irradiation exerted the best antitumor effect among all the treatment groups, revealing the strong synergistic effects of chemo/photothermal/photodynamic therapy. It is worth noting that this DOX/Cy7-hydrogel could almost eliminate the entire tumor masses, significantly prolonging the survival time of tumor-bearing mice over 60 days without detectable adverse effects. Collectively, our findings suggest that this injectable DOX/Cy7-hydrogel with thixotropic and multistimuli responsive properties could be developed as a promising platform for localized and synergistic treatment of cancer.
联合癌症疗法为克服单药治疗的局限性提供了一种有前途的策略，这些局限性包括治疗效果有限、严重的副作用和低生存率。可注射丝素纤维（SF）水凝胶已成为局部治疗的有效平台。本文中，从再生 SF 中提取亲水性 SF（HSF）并在 2-6 小时内自组装成水凝胶。所得 HSF 水凝胶表现出明显的粘弹性、触变性行为和自修复性能。有趣的是，这种水凝胶还表现出对多种因素（酸度、活性氧、谷胱甘肽、热疗和近红外（NIR））的刺激响应药物释放特性，表明其可以根据肿瘤微环境和肿瘤外 NIR 照射实现空间和时间上的按需药物释放。重要的是，瘤内注射载阿霉素（DOX）/Cy7 的 HSF 基水凝胶（DOX/Cy7-水凝胶）加 NIR 照射在所有治疗组中表现出最佳的抗肿瘤效果，显示出化疗/光热/光动力治疗的强烈协同作用。值得注意的是，这种 DOX/Cy7-水凝胶几乎可以消除整个肿瘤块，显著延长荷瘤小鼠的存活时间超过 60 天，且没有可检测到的不良反应。总之，我们的研究结果表明，这种具有触变性和多刺激响应特性的可注射 DOX/Cy7 水凝胶可以作为局部协同治疗癌症的有前途的平台。
