Elemene Hydrogel Modulates the Tumor Immune Microenvironment for Enhanced Treatment of Postoperative Cancer Recurrence and Metastases

Abstract

As a representative active ingredient of traditional Chinese medicine (TCM) and a clinically approved anticancer drug, elemene (ELE) exhibits exciting potential in the antitumor field; however, appropriate drug formulations still need to be explored for specific diseases such as postoperative cancer recurrence and metastasis. Herein, we report an ELE hydrogel with controlled drug release kinetics that can allow ELE to maintain effective concentrations at local lesion sites for extended periods to enhance the bioavailability of ELE. Concretely, dopamine-conjugated hyaluronic acid is synthesized and utilized to prepare ELE nanodrug-embedded hydrogels. In a model of postoperative breast cancer recurrence and metastasis, the ELE hydrogel demonstrates a 96% inhibition rate of recurrence; in contrast, the free ELE nanodrug shows only a 65.5% inhibition rate of recurrence. Importantly, the ELE hydrogel markedly stimulates a potent antitumor immune response in the microenvironment of cancer lesions, increasing antitumor immune cells such as CD8⁺ T cells, CD4⁺ T cells, and M1-type macrophages, as well as elevating antitumor cytokines including TNF-α, IFN-γ, and IL-6. Overall, this study not only advances the field of TCM but also highlights the transformative impact of controlled-release hydrogels in improving antitumor therapy.