Engineering Cannabidiol Synergistic Carbon Monoxide Nanocomplexes to Enhance Cancer Therapy via Excessive Autophagy

Authors

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

Language

English

Publication Date

11-1-2023

Journal

Acta Pharmaceutica Sinica B

DOI

10.1016/j.apsb.2023.05.019

PMID

37969731

PMCID

PMC10638503

PubMedCentral® Posted Date

5-29-2023

PubMedCentral® Full Text Version

Post-print

Abstract

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 comprehensive 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 the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.

Keywords

Carbon monoxide therapy, Cannabidiol, Reactive oxygen species, Excessive autophagy, Autophagic flux, Autolysosome degradation, Metastases, Triple-negative breast cancer

Published Open-Access

yes

Recommended Citation

Xiao, Chang; Sun, Yue; Fan, Jialong; et al., "Engineering Cannabidiol Synergistic Carbon Monoxide Nanocomplexes to Enhance Cancer Therapy via Excessive Autophagy" (2023). Faculty, Staff and Student Publications. 6212.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6212