Zhang Han, Liu Kai, Gong Yimou, Zhu Wenjun, Zhu Jiafei, Pan Feng, Chao Yu, Xiao Zhishen, Liu Yanbin, Wang Xianwen, Liu Zhuang, Yang Yang, Chen Qian
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Centre for Systems Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, the Netherlands.
Biomaterials. 2022 Aug;287:121673. doi: 10.1016/j.biomaterials.2022.121673. Epub 2022 Jul 8.
Vitamin C (VitC) has shown great promise to promote cancer immunotherapy, however, its high hydrophilicity makes it quickly excreted, leading to limited therapeutic efficiency even with frequent high-dose administration. Herein, we provide a pioneering report about the employment of VitC amphiphile self-assembled nanofiber hydrogels for enhanced cancer immunotherapy. Specifically, driven by hydrogen bonding and hydrophobic interactions, the synthesized VitC amphiphile, consisting of a hydrophilic VitC headgroup and a hydrophobic alkyl chain, could self-assemble into an injectable nanofiber hydrogel with self-healing properties. The formed VitC hydrogel not only serves as a reservoir for VitC but also acts as an effective delivery platform for stimulator of interferon genes (STING) agonist-4 (SA). Interestingly, the VitC hydrogel itself exhibits antitumor effects by upregulating genes related to interferon (IFN) signaling, apoptotic signaling and viral recognition and defense. Moreover, the SA-encapsulated VitC hydrogel (SA@VitC hydrogel) synergistically activated the immune system to inhibit the progression of both local and abscopal tumors.
维生素C（VitC）已显示出在促进癌症免疫治疗方面具有巨大潜力，然而，其高亲水性使其迅速排泄，即使频繁高剂量给药，治疗效果也有限。在此，我们提供了一份关于使用VitC两亲性自组装纳米纤维水凝胶增强癌症免疫治疗的开创性报告。具体而言，在氢键和疏水相互作用的驱动下，由亲水性VitC头基和疏水性烷基链组成的合成VitC两亲性分子可自组装成具有自愈特性的可注射纳米纤维水凝胶。形成的VitC水凝胶不仅作为VitC的储存库，还作为干扰素基因（STING）激动剂-4（SA）的有效递送平台。有趣的是，VitC水凝胶本身通过上调与干扰素（IFN）信号传导、凋亡信号传导以及病毒识别和防御相关的基因来发挥抗肿瘤作用。此外，包封SA的VitC水凝胶（SA@VitC水凝胶）协同激活免疫系统，以抑制局部和远隔肿瘤的进展。
