Metal ions-anchored bacterial outer membrane vesicles for enhanced ferroptosis induction and immune stimulation in targeted antitumor therapy

Autor: Ying Sun, Yan-Yan Ma, Shijie Shangguan, Yihang Ruan, Tingjie Bai, Panpan Xue, Huilan Zhuang, Wenyu Cao, Huimei Cai, Enqi Tang, Zhou Wu, Mingzhen Yang, Yixin Zeng, Juan Sun, Yong Fan, Xuemei Zeng, Shuangqian Yan
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-024-02747-3
Popis: Abstract The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H2O2 to •OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.
Databáze: Directory of Open Access Journals
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