College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, China.
Department of Materials Science and Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
Int J Biol Macromol. 2020 Nov 15;163:1208-1222. doi: 10.1016/j.ijbiomac.2020.07.008. Epub 2020 Jul 6.
Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.
具有 pH 敏感性和自修复特性的可注射水凝胶在抗癌药物载体领域具有巨大的应用潜力。在这项工作中，以 4 臂聚乙二醇-苯甲醛（4armPEGDA）和 N-羧乙基壳聚糖（CEC）为原料，制备了一种可注射水凝胶作为新型药物载体。通过改变 4armPEGDA 的浓度，可以调节可注射水凝胶的凝胶时间、平衡溶胀率、降解时间和动态模量。水凝胶在 pH 5.6 时体积收缩，在 pH 7.4 时体积膨胀，有助于控制抗癌药物的释放。在 pH 5.6 时，水凝胶具有快速和显著的 Dox 释放效果，是 pH 7.4 时的五倍。所有水凝胶的体外累积药物释放在第四天左右达到平衡，水凝胶在五天内完全降解，有助于载药水凝胶进一步释放剩余的 Dox。此外，载 Dox 的水凝胶对人肝癌细胞（HepG2）的生长表现出很强的抑制作用。最后，体内抗肿瘤模型实验表明，载 Dox 的水凝胶在五天内可显著抑制肿瘤生长。因此，这种可注射水凝胶是治疗肝癌的潜在理想载体。
