College of Biology, Hunan University, Changsha, 410082, China.
National Centre for Computational Design and Discovery of Novel Materials (MARVEL) and Theory and Simulation of Materials (THEOS), Faculté des Sciences et Techniques de l'Ingénieur, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Acta Biomater. 2022 Jun;145:43-51. doi: 10.1016/j.actbio.2022.04.003. Epub 2022 Apr 8.
Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials, the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.e., self-healing and shear-thinning, as an injectable localized drug delivery platform. The drug-encapsulating MOF hydrogel is formed through a dynamic coordination bond cross-linkage between a doxorubicin-loaded MOF (MOF@DOX) particle and a homemade bisphosphonate-modified hyaluronic acid (HA-BP) polymeric binder. The HA-BP·MOF@DOX hydrogel demonstrates pH- and ATP-responsive drug release characteristic and efficiently kills cancer cells in vitro. The animal experiments reveal that the HA-BP·MOF@DOX hydrogel has enhanced capability in terms of tumor growth suppression as compared to the MOF@DOX group, which can be attributed to drug localization in hydrogel superstructure and sustained release at the tumor site. The presented injectable dynamic MOF-based hydrogel is a promising in vivo localized drug delivery system for cancer treatment. Herein, we report the self-healing and shear-thinning of MOF-based drug carrier cross-linked by coordinate bonds for the first time and provide new insights and a facile chemical strategy for designing and fabricating MOF-based biomaterials by using bisphosphonate-zinc interaction. STATEMENT OF SIGNIFICANCE: Bisphosphonate-zinc interaction is a facile chemical strategy to cross-link metal-organic framework (MOF)-based hydrogel. The presented MOF-based hydrogel demonstrates structurally dynamic properties, including smooth injectability, self-healing, and shear-thinning. The developed MOF-based hydrogel possesses pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The dynamic MOF-based hydrogel shows enhanced in vivo anticancer activity as compared to pure MOF particles. Self-healing and shear-thinning of metal-ligand cross-linked MOF-based drug delivery system are reported for the first time, thus providing new insights for the design and fabrication of MOF-based biomaterials.
金属有机骨架（MOF）是一类令人兴奋的多孔生物材料，被认为是储存和输送治疗药物的载体。然而，与其他纳米材料一样，MOF 在临床环境中的应用仍然受到限制，因为其有效载荷过早扩散和组织靶向行为异常。为了克服这些挑战，我们设计了一种具有结构动态特性的基于 MOF 的水凝胶，即自修复和剪切变稀，作为可注射的局部药物递送平台。载药 MOF 水凝胶是通过载阿霉素的 MOF（MOF@DOX）颗粒与自制的双膦酸盐修饰透明质酸（HA-BP）聚合物结合剂之间的动态配位键交联形成的。HA-BP·MOF@DOX 水凝胶表现出 pH 和 ATP 响应性药物释放特性，并在体外有效杀死癌细胞。动物实验表明，与 MOF@DOX 组相比，HA-BP·MOF@DOX 水凝胶在抑制肿瘤生长方面具有更强的能力，这归因于药物在水凝胶超结构中的定位和在肿瘤部位的持续释放。所提出的可注射动态 MOF 基水凝胶是一种有前途的用于癌症治疗的体内局部药物递送系统。在这里，我们首次报道了通过配位键交联的基于 MOF 的药物载体的自修复和剪切变稀，并提供了一种新的见解和简便的化学策略，用于通过双膦酸盐-锌相互作用设计和制造基于 MOF 的生物材料。 意义声明：双膦酸盐-锌相互作用是一种简便的化学策略，可用于交联基于金属有机骨架（MOF）的水凝胶。所提出的基于 MOF 的水凝胶表现出结构动态特性，包括光滑的可注射性、自修复和剪切变稀。所开发的基于 MOF 的水凝胶具有 pH 和 ATP 响应性药物释放特性，并能有效杀死体外癌细胞。与纯 MOF 颗粒相比，动态基于 MOF 的水凝胶显示出增强的体内抗癌活性。金属-配体交联的 MOF 基药物递送系统的自修复和剪切变稀特性首次被报道，从而为 MOF 基生物材料的设计和制备提供了新的见解。
