Local drug delivery systems, especially hydrogels, show superior strengths in postoperative recurrence prevention. Despite great advances, clinical translation of the hydrogels has been largely restricted as these drug delivery systems generally require chemical modification or additional carrier molecules to form hydrogels, which results in side effects correlative with local inflammation and systemic toxicity. Here, we developed a pure molecular anticancer drug hydrogel that reduced post-surgical tumor recurrence. The macroscopic pure molecular hydrogel was generated via ultrasonication of anticancer drug raltitrexed in aqueous solution, which was facile and environmentally friendly without involving chemical synthesis. Molecular dynamics simulations confirmed that raltitrexed self-assembled into a nanofibrous hydrogel through hydrogen bond and π-π interaction. Delivered as a hydrogel, raltitrexed could effectively decrease tumor recurrence rate and promote the inhibition of tumor growth in vivo. This raltitrexed self-delivery hydrogel has the potential to serve as a powerful auxiliary implement for preventing postoperative local tumor recurrence.

局部药物输送系统，尤其是水凝胶，在预防术后复发方面显示出优越的优势。尽管取得了很大进展，但是由于这些药物递送系统通常需要化学修饰或另外的载体分子来形成水凝胶，因此水凝胶的临床翻译受到了很大的限制，这导致了与局部炎症和全身毒性有关的副作用。在这里，我们开发了一种纯净的分子抗癌药物水凝胶，可减少手术后肿瘤的复发。宏观纯分子水凝胶是通过超声处理在水溶液中复溶的抗癌药物而生成的，其简便易行且对环境友好，且无需化学合成。分子动力学模拟证实了拉替曲曲通过氢键和π-π相互作用自组装成纳米纤维水凝胶。作为水凝胶提供，raltitrexed可有效降低肿瘤复发率并促进对肿瘤生长的抑制体内。这种雷特雷克斯自输送水凝胶有潜力作为预防术后局部肿瘤复发的有力辅助工具。