In this work, novel biocompatible and reduction-responsive soft hydrogels were formulated from norbornene (Nb)-functionalized carboxymethyl cellulose (CMCNb). To cross-link the CMC-Nb via a highly bioorthogonal inverse electron demand Diels–Alder (IEDDA) reaction, we employed a water-soluble and reduction-responsive diselenide-based cross-linker possessing two terminal tetrazine (Tz) groups with varying molar concentrations (Nb/Tz molar ratios of 10/10, 10/05, and 10/2.5). The N₂ microbubbles liberated as a by-product during the IEDDA reaction generated in-situ pores in hydrogel networks. The resulting hydrogels had highly porous structures and relatively soft mechanical properties (storage moduli in the range 74 ⁓160 Pa). The hydrogels showed high swelling ratios (>35 times), tunable gelation times (1–5 min), and excellent doxorubicin (DOX) loading efficiencies (>85 %). The hydrogels exhibited stimuli-responsive and fast release of DOX (99 %, after 12 h) in the presence of 10 mmol of glutathione as compared to the normal PBS solution (38 %). The cytotoxic effects of blank hydrogels were not observed against HEK-239 cells, while the DOX-encapsulated hydrogels exhibited anti-tumor activity in BT-20 cancer cells. The results indicate potential applications of the CMC-based soft hydrogels in injectable drug delivery systems.

在这项工作中，由降冰片烯 (Nb) 官能化的羧甲基纤维素 (CMC Nb) 配制出新型的生物相容性和还原响应性软水凝胶。为了通过高度生物正交的逆电子需求 Diels-Alder (IEDDA) 反应交联 CMC-Nb ，我们采用了水溶性和还原响应型二硒化物基交联剂，该交联剂具有两个末端四嗪 (Tz) 基团，摩尔数不同浓度（Nb/Tz 摩尔比为 10/10、10/05 和 10/2.5）。在原位产生的 IEDDA 反应过程中作为副产物释放的 N _2微泡水凝胶网络中的孔隙。所得水凝胶具有高度多孔的结构和相对柔软的机械性能（存储模量在 74⁓160 Pa 范围内）。水凝胶表现出高溶胀率（>35 倍）、可调节的凝胶时间（1-5 分钟）和出色的阿霉素（DOX）负载效率（>85%）。与正常 PBS 溶液 (38%) 相比, 在 10 mmol 谷胱甘肽存在下, 水凝胶表现出刺激响应和 DOX 的快速释放 (99%, 12 小时后)。未观察到空白水凝胶对 HEK-239 细胞的细胞毒性作用，而 DOX 包封的水凝胶在 BT-20 癌细胞中表现出抗肿瘤活性。结果表明基于 CMC 的软水凝胶在注射给药系统中的潜在应用。