Hubei Engineering Center of Natural Polymer-Based Medical Materials, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Acta Biomater. 2022 Mar 15;141:102-113. doi: 10.1016/j.actbio.2021.12.036. Epub 2022 Jan 3.
Tumor local chemotherapy employing injectable hydrogel reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remain appealing challenges. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels (CAAs) dressed with self-healing properties, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between β-cyclodextrin (CD) and 1-adamantane (AD), the hydrogels exhibited injectability, self-healing properties (healing efficiency of 97.5%) and rapid recovery (< 10 min) without external stimuli in physiological environment. Moreover, the hydrogels equipped with dynamic acylhydrazone linkages underwent slow hydrolytic degradation (> 30 days) and pH-responsive behavior, endowing the hydrogels with precise spatiotemporal drug release administration. The in vivo application of CAA as a carrier was studied using doxorubicin (DOX) model drug, and the results shows that using CAA as DOX carrier not only greatly enhances the anti-tumor efficacy of DOX, but also reduced the side effects of DOX. STATEMENT OF SIGNIFICANCE: With the preassemble approach combining host-guest interactions with dynamic acylhydrazone bonds, this work demonstrated a multi-functional self-healing hydrogel as drug carrier developed by using natural polysaccharides, which offers a new avenue for the high-value utilization of biomass. The strategy demonstrated in the present work may also supply a pathway for the preparation and regulation of hydrogels as intelligent biomedicine materials.
利用可注射水凝胶储库进行肿瘤局部化疗是实现精确给药的一种很有前途的平台。然而，自修复水凝胶的平衡可注射性、pH 响应性和长期水解稳定性仍然是一个吸引人的挑战。在此，通过主客体相互作用与动态酰腙键相结合的模块化预组装策略，用于构建具有自修复性能、pH 响应性和水解稳定性的可注射纤维素基水凝胶（CAAs）。由于β-环糊精（CD）和 1-金刚烷（AD）之间的主客体相互作用，水凝胶在生理环境中无需外部刺激即可表现出可注射性、自修复性能（愈合效率为 97.5%）和快速恢复（<10 min）。此外，具有动态酰腙键的水凝胶经历缓慢的水解降解（>30 天）和 pH 响应行为，使水凝胶能够精确控制药物的时空释放。以阿霉素（DOX）模型药物为例，研究了 CAA 作为载体的体内应用，结果表明，使用 CAA 作为 DOX 载体不仅大大提高了 DOX 的抗肿瘤疗效，而且降低了 DOX 的副作用。 意义声明：通过主客体相互作用与动态酰腙键相结合的预组装方法，本工作展示了一种多功能自修复水凝胶作为药物载体，该载体由天然多糖制备而成，为生物质的高值化利用提供了新途径。本工作中展示的策略也可能为智能生物医学材料的水凝胶的制备和调控提供一条途径。
