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Fujie Jiang,1,2,* Lu Wang,1,* Yu Tang,1 Yaotai Wang,1 Ningshan Li,1,3 Disen Wang,1 Zhong Zhang,1 Li Lin,1 Yan Du,1 Xia Ou,1 Jianzhong Zou1 1State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 3Department of Ultrasound, Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzhong Zou, State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86-13708302390, Email zoujzh@cqmu.edu.cnPurpose: Breast cancer is detrimental to the health of women due to the difficulty of early diagnosis and unsatisfactory therapeutic efficacy of available breast cancer therapies. High intensity focused ultrasound (HIFU) ablation is a new method for the treatment of breast tumors, but there is a problem of low ablation efficiency. Therefore, the improvement of HIFU efficiency to combat breast cancer is immediately needed. This study aimed to describe a novel anaerobic bacteria-mediated nanoplatform, comprising synergistic HIFU therapy for breast cancer under guidance of ultrasound (US) and magnetic resonance (MR) bimodal imaging.Methods: The PFH@CL/Fe3O4 nanoparticles (NPs) (Perfluorohexane (PFH) and superparamagnetic iron oxides (SPIO, Fe3O4) with cationic lipid (CL) NPs) were synthesized using the thin membrane hydration method. The novel nanoplatform Bifidobacterium bifidum-mediated PFH@CL/Fe3O4 NPs were constructed by electrostatic adsorption. Thereafter, US and MR bimodal imaging ability of

Fujie Jiang,1,2,* Lu Wang,1,* Yu Tang,1 Yaotai Wang,1 Ningshan Li,1,3 Disen Wang,1 Zhong Zhang,1 Li Lin,1 Yan Du,1 Xia Ou,1 Jianzhong Zou1 1State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 3Department of Ultrasound, Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianzhong Zou, State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86-13708302390, Email zoujzh@cqmu.edu.cnPurpose: Breast cancer is detrimental to the health of women due to the difficulty of early diagnosis and unsatisfactory therapeutic efficacy of available breast cancer therapies. High intensity focused ultrasound (HIFU) ablation is a new method for the treatment of breast tumors, but there is a problem of low ablation efficiency. Therefore, the improvement of HIFU efficiency to combat breast cancer is immediately needed. This study aimed to describe a novel anaerobic bacteria-mediated nanoplatform, comprising synergistic HIFU therapy for breast cancer under guidance of ultrasound (US) and magnetic resonance (MR) bimodal imaging.Methods: The PFH@CL/Fe3O4 nanoparticles (NPs) (Perfluorohexane (PFH) and superparamagnetic iron oxides (SPIO, Fe3O4) with cationic lipid (CL) NPs) were synthesized using the thin membrane hydration method. The novel nanoplatform Bifidobacterium bifidum-mediated PFH@CL/Fe3O4 NPs were constructed by electrostatic adsorption. Thereafter, US and MR bimodal imaging ability of

Yu Tang, Chun Chen, Binglei Jiang, Lu Wang, Fujie Jiang, Disen Wang, Yaotai Wang, Haiyan Yang, Xia Ou, Yan Du, Qi Wang, Jianzhong Zou State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chem

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 +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: 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.

Yu Tang, Chun Chen, Binglei Jiang, Lu Wang, Fujie Jiang, Disen Wang, Yaotai Wang, Haiyan Yang, Xia Ou, Yan Du, Qi Wang, Jianzhong Zou State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chem

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 +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: 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.

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting a

Yaotai Wang,1 Chun Chen,1 Yong Luo,1 Jie Xiong,1 Yu Tang,1 Haiyan Yang,1 Lu Wang,1 Fujie Jiang,1 Xuan Gao,2 Die Xu,2 Huanan Li,1 Qi Wang,1 Jianzhong Zou1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Jianzhong ZouState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel +86-13708302390Email zoujzh@cqmu.edu.cnPurpose: The high-intensity focused ultrasound (HIFU) ablation of tumors is inseparable from synergistic agents and image monitoring, but the existing synergistic agents have the defects of poor targeting and a single imaging mode, which limits the therapeutic effects of HIFU. The construction of a multifunctional biological targeting synergistic agent with high biosafety, multimodal imaging and targeting therapeutic performance has great significance for combating cancer.Methods: Multifunctional biological targeting synergistic agent consisting of Bifidobacterium longum (B. longum), ICG and PFH coloaded cationic lipid nanoparticles (CL-ICG-PFH-NPs) were constructed for targeting multimode imaging, synergistic effects with HIFU and imaging-guided ablation of tumors, which was evaluated both in vitro and in vivo.Results: Both in vitro and in vivo systematical studies validated that the biological targeting synergistic agent can simultaneously achieve tumor-biotargeted multimodal imaging, HIFU synergism and multimodal image monitoring in HIFU therapy. Importantly, the electrostatic adsorption method and the targeting of B. longum to tumor tissues allow the CL-ICG-PFH-NPs to be retained in the tumor tissue, achieve the targeting a