Genetically Engineered Bacterial Protein Nanoparticles for Targeted Cancer Therapy
Haiyan Yang, Fujie Jiang, Xiaojuan Ji, Lu Wang, Yaotai Wang, Liang Zhang, Yu Tang, Disen Wang, Yong Luo, Ningshan Li, Qi Wang, Jianzhong Zou
Abstract
Purpose: 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