Elemene Hydrogel Modulates\nthe Tumor Immune Microenvironment\nfor Enhanced Treatment of Postoperative Cancer Recurrence and Metastases

As a representative active ingredient of traditional\nChinese medicine\n(TCM) and a clinically approved anticancer drug, elemene (ELE) exhibits\nexciting potential in the antitumor field; however, appropriate drug\nformulations still need to be explored for specific diseases such\nas postoperative cancer recurrence and metastasis. Herein, we report\nan ELE hydrogel with controlled drug release kinetics that can allow\nELE to maintain effective concentrations at local lesion sites for\nextended periods to enhance the bioavailability of ELE. Concretely,\ndopamine-conjugated hyaluronic acid is synthesized and utilized to\nprepare ELE nanodrug-embedded hydrogels. In a model of postoperative\nbreast cancer recurrence and metastasis, the ELE hydrogel demonstrates\na 96% inhibition rate of recurrence; in contrast, the free ELE nanodrug\nshows only a 65.5% inhibition rate of recurrence. Importantly, the\nELE hydrogel markedly stimulates a potent antitumor immune response\nin the microenvironment of cancer lesions, increasing antitumor immune\ncells such as CD8<sup>+</sup> T cells, CD4<sup>+</sup> T cells, and\nM1-type macrophages, as well as elevating antitumor cytokines including\nTNF-α, IFN-γ, and IL-6. Overall, this study not only advances\nthe field of TCM but also highlights the transformative impact of\ncontrolled-release hydrogels in improving antitumor therapy.