Sundarakrishnan Aswin
Department of Materials Science & Biomedical Engineering, University of Wisconsin Eau Claire, Eau Claire, WI 54701, USA.
Gels. 2025 Apr 14;11(4):288. doi: 10.3390/gels11040288.
Systemic chemotherapy is still the first-line treatment for cancer, and it's associated with toxic side effects, chemoresistance, and ultimately cancer recurrence. Rapid gelling hydrogels can overcome this limitation by providing localized delivery of anti-cancer agents to solid tumors. Silk hydrogels are extremely biocompatible and suitable for anti-cancer drug delivery, but faster gelling formulations are needed. In this study, we introduce a rapid gelling hydrogel formulation (<3 min gelling time) due to chemical crosslinking between silk fibroin and curcumin, initiated by the addition of minute quantities of horseradish peroxidase (HRP) and hydrogen peroxide (HO). The novel observation in this study is that curcumin, while being a free-radical scavenger, also participates in accelerating silk di-tyrosine crosslinking in the presence of HRP and HO. Using UV-Vis, rheology, and time-lapse videos, we convincingly show that curcumin accelerates silk di-tyrosine crosslinking reaction in a concentration-dependent manner, and curcumin remains entrapped in the hydrogel post-crosslinking. FTIR results show an increase in secondary beta-sheet structures within hydrogels, with increasing concentrations of curcumin. Furthermore, we show that curcumin-silk di-tyrosine hydrogels are toxic to U2OS osteosarcoma cells, and most cancer cells are dead within short time scales of 4 h post-encapsulation.
全身化疗仍然是癌症的一线治疗方法，但其存在毒副作用、化疗耐药性，并最终导致癌症复发。快速凝胶化水凝胶可以通过将抗癌药物局部递送至实体瘤来克服这一局限性。丝素水凝胶具有极高的生物相容性，适用于抗癌药物递送，但需要更快的凝胶化配方。在本研究中，我们通过添加微量辣根过氧化物酶（HRP）和过氧化氢（HO）引发丝素蛋白与姜黄素之间的化学交联，引入了一种快速凝胶化水凝胶配方（凝胶化时间<3分钟）。本研究中的新发现是，姜黄素虽然是一种自由基清除剂，但在HRP和HO存在的情况下，它也参与加速丝素双酪氨酸交联。通过紫外可见光谱、流变学和延时视频，我们令人信服地表明姜黄素以浓度依赖的方式加速丝素双酪氨酸交联反应，并且姜黄素在交联后仍被困在水凝胶中。傅里叶变换红外光谱结果表明，随着姜黄素浓度的增加，水凝胶中的二级β-折叠结构增加。此外，我们表明姜黄素-丝素双酪氨酸水凝胶对U2OS骨肉瘤细胞有毒性，并且大多数癌细胞在包封后4小时的短时间内死亡。
