A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Jingya Zhao; Huabei Huang; Jinyan Zhao; Xiang Xiong; Sibo Zheng; Xiaoqing Wei; Shaobing Zhou

doi:10.1016/j.apsb.2021.10.019

A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Acta Pharm Sin B. 2022 Jun;12(6):2683-2694. doi: 10.1016/j.apsb.2021.10.019. Epub 2021 Oct 26.

Authors

Jingya Zhao¹, Huabei Huang¹, Jinyan Zhao¹, Xiang Xiong¹, Sibo Zheng¹, Xiaoqing Wei¹, Shaobing Zhou¹

Affiliation

¹ Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

Abstract

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag₂S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

Keywords: 4T1 cells, mouse mammary 4T1 tumor cells; AgNO3, silver nitrate; B.b, Bifidobacterium bifidum; B.b@QDs, hybrid bacteria; Bifidobacterium; CRT, calreticulin; CTLs, cytotoxic T lymphocytes; DLS, dynamic light scattering; EC cells, endothelial cells; GC, glycol chitosan; GSH, reduced glutathione; H&E, hematoxylin‒eosin; ICD, immunogenic cell death; Immunogenic cell death; Immunotherapy; Na2S, sodium sulfide; QDs, quantum dots; Quantum dot; TAMs, tumor-associated macrophages; TEM, transmission electron microscopy; TUNEL, transferase-mediated UTP end labeling; Tumor-associated macrophage; XRD, X-ray diffraction.