Bacteria-based Cascade Near-infrared Nano-optogenetically Induced Photothermal Tumor Therapy

Overview

Journal Theranostics

Date 2024 Sep 13

PMID 39267783

Authors

Xiuwen Hu

Jiawen Chen

Yuzhi Qiu

Sihan Chen

Yidi Liu

Xi Yu

Yunting Liu

Xiangliang Yang

Yan Zhang

Yanhong Zhu

Affiliations

Soon will be listed here.

Abstract

Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcN-UCNPs) for enhanced tumor therapy. EcN-UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcN-UCNPs were determined in both H22 and 4T1 tumors. The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an photothermal agent in tumors. The formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcN-UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response. Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.

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