Journal
ACTA PHARMACEUTICA SINICA B
Volume 12, Issue 6, Pages 2683-2694Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.10.019
Keywords
Immunotherapy; Tumor-associated macrophage; Immunogenic cell death; Bifidobacterium; Quantum dot
Categories
Funding
- National Natural Science Foundation of China [51725303, 81701831, 52033007]
- Sichuan Science and Technology Program (China) [2020YFH0046]
- Fundamental Research Funds for the Central Universities (China) [2682021CG017]
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Researchers have developed a hybrid bacterium that targets tumors and modifies tumor-associated macrophages, improving the effectiveness of immunotherapy for cancer treatment.
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.
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