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.

中文翻译：

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Elemene 水凝胶调节肿瘤免疫微环境以增强术后癌症复发和转移的治疗


榄香烯 （ELE） 作为中药 （TCM） 的代表性活性成分和临床批准的抗癌药物，在抗肿瘤领域显示出令人兴奋的潜力;然而，仍需针对特定疾病（如术后癌症复发和转移）探索合适的药物配方。在此，我们报道了一种具有受控药物释放动力学的 ELE 水凝胶，它可以使 ELE 在局部病变部位长时间保持有效浓度，以提高 ELE 的生物利用度。具体来说，合成多巴胺偶联的透明质酸并用于制备 ELE 纳米药物包埋的水凝胶。在术后乳腺癌复发和转移的模型中，ELE 水凝胶显示出 96% 的复发抑制率;相比之下，游离 ELE 纳米药物的复发抑制率仅为 65.5%。重要的是，ELE 水凝胶在癌症病灶的微环境中显着刺激有效的抗肿瘤免疫反应，增加抗肿瘤免疫细胞，如 CD8⁺ T 细胞、CD4⁺ T 细胞和 M1 型巨噬细胞，以及升高抗肿瘤细胞因子，包括 TNF-α、IFN-γ 和 IL-6。总体而言，这项研究不仅推动了中医领域的发展，还强调了控释水凝胶在改善抗肿瘤治疗方面的变革性影响。