Hypoxia-targeted and spatial-selective tumor suppression by near infrared nanoantenna sensitized engineered bacteria

Chengcheng Tao; Xinxing Miao; Jun Yan; Xiang Xiao; Renfei Wu; Qinghua Cao; Zhexiang Wang; Rui Lv; Tianjin Ge; Jian Liu

doi:10.1016/j.actbio.2023.08.044

Hypoxia-targeted and spatial-selective tumor suppression by near infrared nanoantenna sensitized engineered bacteria

Acta Biomater. 2023 Oct 15:170:442-452. doi: 10.1016/j.actbio.2023.08.044. Epub 2023 Aug 25.

Authors

Chengcheng Tao¹, Xinxing Miao¹, Jun Yan², Xiang Xiao¹, Renfei Wu¹, Qinghua Cao¹, Zhexiang Wang¹, Rui Lv¹, Tianjin Ge¹, Jian Liu³

Affiliations

¹ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China.
² Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: jyan2020@suda.edu.cn.
³ Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: jliu@suda.edu.cn.

PMID: 37634834
DOI: 10.1016/j.actbio.2023.08.044

Abstract

It is an active research area in the development of engineered bacteria to address the bottleneck issue of hypoxic tumors, which otherwisely possess resistance to chemotherapies, radiotherapies, and photodynamic therapies. Here we report a new method to ablate hypoxic tumors with NIR-nanoantenna sensitized engineered bacteria (NASEB) in a highly effective and dual selective manner. It features engineered E. coli MG1655 (EB) with coatings of lanthanide upconversion nanoparticles (UCNPs) as external antennas on bacterial surface (MG1655/HlyE-sfGFP@UCNP@PEG), enabling NIR laser-switchable generation/secretion of HlyE perforin to kill cancer cells. We have demonstrated that NASEB enrichment on hypoxic tumor sites via their innate chemotactic tendency, in assistance of localized NIR laser irradiation, can suppress tumors with improved efficacy and selectivity, thus minimizing potential side effects in cancer treatment. The NIR-responsive nanoantenna sensitized switching in engineering bacteria is distinct from the previous reports, promising conceptually new development of therapeutics against hypoxic tumors. STATEMENT OF SIGNIFICANCE: Tumor hypoxia exacerbates tumor progression, but also reduces the efficacy of conventional chemotherapies, radiotherapies, or photodynamic therapies. Here we develop near infrared Nano Antenna Sensitized Engineered Bacteria (NASEB) to treat hypoxic tumors. NASEB can accumulate and proliferate on hypoxic tumor sites via their innate chemotactic tendency. After receiving NIR laser signals, the upconversion nanoparticles on NASEB surface as antennas can transduce them to blue light for activation of HlyE perforin in the protein factory of EB. Our method features dual selectivity on the tumor sites, contributed by hypoxic tumor homing of anaerobic bacteria and spatial confinement through selective NIR laser irradiation. The concept of NASEB promises to address the challenges of tumor hypoxia for cancer therapies.

Keywords: Cancer therapy; Engineered bacteria; Hypoxic tumors; Nanoparticles; Near infrared.