Genetically Engineered Bacterial Protein Nanoparticles for Targeted Cancer Therapy

Abstract

Haiyan Yang,1 Fujie Jiang,1 Xiaojuan Ji,2 Lu Wang,1 Yaotai Wang,1 Liang Zhang,3 Yu Tang,1 Disen Wang,1 Yong Luo,1 Ningshan Li,1 Qi Wang,1 Jianzhong Zou1 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Ultrasound, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical and Research Center of Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400016, People’s Republic of China; 3Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, Yuzhong District 400016, People’s Republic of ChinaTel [phone]Email [email protected]: Cancer treatment still faces big challenges in the clinic, which is raising concerns over the world. In this study, we report the novel strategy of combing bacteriotherapy with high-intensity focused ultrasound (HIFU) therapy for more efficient breast cancer treatment.Methods: The acoustic reporter gene (ARG) was genetically engineered to be expressed successfully in Escherichia coli (E. coli) to produce the protein nanoparticles-gas vesicles (GVs). Ultrasound was utilized to visualize the GVs in E. coli. In addition, it was injected intravenously for targeted breast cancer therapy by combing the bacteriotherapy with HIFU therapy.Results: ARG expressed in E. coli can be visualized in vitro and in vivo by ultrasound. After intravenous injection, E. coli containing GVs could specifically target the tumor site, colonize consecutively in the tumor microenvironment, and it could obviously inhibit tumor growth. Meanwhile, E. coli which contained GVs could synergize HIFU therapy efficiently both in vitro and in vivo as the cavitation nuclei. Furthermore, the tumor inhibition rate in the combination therapy group could be high up to 87% compared with that in the control group.Conclusion: Our novel strategy of combing bacteriotherapy with HIFU therapy can treat breast cancers more effectively than the monotherapies, so it can be seen as a promising strategy.Keywords: acoustic reporter gene, gas vesicles, targeted cancer therapy, bacteriotherapy, high-intensity focused ultrasound

Keywords

• acoustic reporter gene
• gas vesicles
• targeted cancer therapy
• bacteriotherapy
• high-intensity focused ultrasound