State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
Nanoscale. 2017 Sep 28;9(37):14058-14064. doi: 10.1039/c7nr04990k.
Inflammatory responses play crucial roles in the development and progression of tumors. Tumor-associated inflammation not only promotes tumor growth but also induces the suppression of immune responses against tumors. We demonstrate in this study that hydrogels of nonsteroidal anti-inflammatory drug (NSAID) modified D-tetrapeptides (GFFY) are promising cancer vaccine adjuvants, especially for Fbp-gel and Car-gel. The hydrogels allow easy incorporation of a protein OVA antigen by vortexing. Our results indicate that vaccines based on Fbp-gel and Car-gel increase IgG production by 1476- and 929-fold, compared with the OVA group, respectively. They exhibit higher IgG2a antibody titers and stimulate the production of IFN-γ and IL-6 cytokines. Their higher antibody and cytokine eliciting properties in combination with their anti-inflammatory properties endow them with excellent tumor elimination properties in vivo. In a preventive immune assay against B16-OVA tumors, they totally prevent tumorigenesis. In a therapeutic immune assay against EG7-OVA tumors, they inhibit tumor growth by 75%, compared with the PBS group. Our results suggest the great potential of our hydrogels in the development of vaccines to treat cancers.
炎症反应在肿瘤的发生和发展中起着至关重要的作用。肿瘤相关炎症不仅促进肿瘤生长，还诱导对肿瘤的免疫反应抑制。在本研究中，我们证明了非甾体抗炎药（NSAID）修饰的 D-四肽（GFFY）水凝胶是有前途的癌症疫苗佐剂，特别是对于 Fbp-凝胶和 Car-凝胶。水凝胶允许通过涡旋轻松掺入蛋白质 OVA 抗原。我们的结果表明，基于 Fbp-凝胶和 Car-凝胶的疫苗分别比 OVA 组增加了 1476 倍和 929 倍的 IgG 产生。它们表现出更高的 IgG2a 抗体滴度，并刺激 IFN-γ 和 IL-6 细胞因子的产生。它们具有更高的抗体和细胞因子引发特性以及抗炎特性，使它们具有出色的体内肿瘤消除特性。在针对 B16-OVA 肿瘤的预防性免疫检测中，它们完全阻止了肿瘤发生。在针对 EG7-OVA 肿瘤的治疗性免疫检测中，它们与 PBS 组相比抑制了 75%的肿瘤生长。我们的结果表明，我们的水凝胶在开发治疗癌症的疫苗方面具有巨大的潜力。
