Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy

文献类型： 外文期刊

第一作者： Xiao, Chang

作者： Xiao, Chang;Sun, Yue;Fan, Jialong;Chen, Simin;Long, Ying;Liu, Bin;Sun, Yue;Zhu, Aiguo;Nguyen, William;Chen, Wei

作者机构：

关键词： Carbon monoxide therapy; Cannabidiol; Reactive oxygen species; Excessive autophagy; Autophagic flux; Autolysosome degradation; Metastases; Triple-negative breast cancer

期刊名称：ACTA PHARMACEUTICA SINICA B （ 影响因子：14.5； 五年影响因子：13.2 ）

ISSN： 2211-3835

年卷期： 2023 年 13 卷 11 期

页码：

收录情况： SCI

摘要： Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The compre-hensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, HMPOC@M-mediated excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that HMPOC@M+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance he efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.

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