Living hybrid material based on probiotic with photothermal properties inhibits PD-L1 expression after tumouricidal photothermal therapy.

Abstract

Photothermal therapy is a safe and effective tumour treatment strategy due to its excellent spatiotemporal controllability. However, interferon gamma in the tumour microenvironment is upregulated after photothermal therapy, which enhances the expression of programmed cell death ligand 1 (PD-L1) in tumour cells. This further promotes immunosuppression and tumour metastasis, resulting in a poor prognosis in cancer therapy. Traditional nanodrugs often face challenges in penetrating the dense extracellular matrix of solid tumours, whereas certain probiotics possess the ability to specifically colonise the core regions of tumours. In this research, we used Escherichia coli Nissle 1917 (ECN) as a chassis cell and self-assembly polydopamine (PDA) on the ECN surface. The black PDA@ECN (notes as PE) actively colonises at the tumour site and produces a photothermal effect under 808 nm laser irradiation to kill tumour cells. To overcome the high expression of PD-L1 induced after photothermal therapy, metformin (MET) was also encapsulated in PE to form PDA@MET@ECN (notes as PME). In vivo experiments demonstrated that PME effectively inhibited the PD-L1 expression and growth of CT26 tumour cells. Overall, PME reverses the immunosuppressive tumour microenvironment and enhances the effect of photothermal/immune therapy in tumour treatment.