Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, P. R. China.
Org Biomol Chem. 2019 Apr 10;17(15):3853-3860. doi: 10.1039/c9ob00046a.
Drug incorporation in hydrogels often brings undesirable effects on the stability or mechanical properties of the system. To address this problem, we report the design and synthesis of a RGD-derived peptide conjugate (1-RGDH) for its co-assembly with a commonly used chemotherapeutic drug, doxorubicin (DOX), that formed electrostatic interactions with the 1-RGDH peptide and reinforced the supramolecular network of nanofibers within the matrix of the hydrogel. The hybrid hydrogel demonstrated excellent viscoelastic and shear-thinning properties that greatly facilitated the development of injectable drug delivery systems. Furthermore, it demonstrated a unique pH responsive release of DOX under weakly acidic conditions, paving ways for the controlled release of drug cargos in a typical tumor microenvironment with mild acidity. Finally, the DOX-incorporated hydrogel exhibited a superior anti-tumor efficacy in non-small-cell lung cancer cells A549 compared to the aqueous solution of free DOX, with an integrin receptor-mediated endocytosis pathway revealed for the cellular uptake of DOX-incorporated nanofibers.
水凝胶中药物的掺入常常会对体系的稳定性或机械性能产生不良影响。为了解决这个问题，我们设计并合成了一种 RGD 衍生的肽缀合物（1-RGDH），用于与一种常用的化疗药物阿霉素（DOX）共组装，DOX 通过静电相互作用与 1-RGDH 肽结合，并增强了水凝胶基质中纳米纤维的超分子网络。这种杂化水凝胶表现出优异的粘弹性和剪切稀化性能，极大地促进了可注射药物输送系统的发展。此外，它在弱酸性条件下表现出独特的 DOX 响应性释放，为在具有轻度酸性的典型肿瘤微环境中控制药物载体的释放铺平了道路。最后，与游离 DOX 的水溶液相比，载 DOX 的水凝胶在非小细胞肺癌细胞 A549 中表现出优异的抗肿瘤功效，揭示了整合素受体介导的内吞途径用于细胞摄取载 DOX 的纳米纤维。
