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Injectable, Thixotropic, and Multiresponsive Silk Fibroin Hydrogel for Localized and Synergistic Tumor Therapy
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-01-13 , DOI: 10.1021/acsbiomaterials.9b01676
Shuangquan Gou 1, 2 , Dengchao Xie 2, 3 , Ya Ma 2 , Yamei Huang 2 , Fangyin Dai 1, 4 , Chenhui Wang 5 , Bo Xiao 1, 4
Affiliation  

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.

中文翻译:

可注射的,触变的和多反应的丝素蛋白水凝胶,用于局部和协同肿瘤治疗

联合癌症疗法为克服单一药物治疗的局限性提供了一种有前途的策略,这些局限性包括疗效有限,严重的副作用和低生存率。注射用丝素蛋白(SF)水凝胶已成为局部治疗的有效平台。本文中,从再生的SF中提取了亲水性SF(HSF),并在2到6小时内将其自组装成水凝胶。所得的HSF水凝胶显示出明显的粘弹性,触变性和自修复性能。有趣的是,当受到多种因素(酸度,活性氧,谷胱甘肽,高温和近红外(NIR))触发时,这种水凝胶还表现出出色的刺激响应药物释放曲线,提示它可以实现对肿瘤微环境和肿瘤外NIR辐射的时空按需药物释放。重要的是,瘤内注射阿霉素(DOX)/ Cy7的HSF基水凝胶(DOX / Cy7-水凝胶)加上NIR辐射在所有治疗组中均表现出最佳的抗肿瘤效果,显示出化学/光热/光动力疗法的强大协同作用。值得一提的是,这种DOX / Cy7水凝胶几乎可以消除整个肿瘤块,从而显着延长了荷瘤小鼠的存活时间超过60天,而没有发现不良影响。总的来说,
更新日期:2020-01-13
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