Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy

Background High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual...

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Main Authors: Ying Zhou, Chen Cheng, Qi Wang, Min Zheng, Pan Li, Yang Zhou, Yuting Cao, Li Wan, Xun Guo, Xiaohong Lin, Rui Tang, Hongye He, Nianhong Wu, Qiaoqi Chen, Yaqin Hu, Xialin Xiong, Faqi Li
Format: Article
Language:English
Published: BMJ Publishing Group 2023-01-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/11/1/e006226.full
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author Ying Zhou
Chen Cheng
Qi Wang
Min Zheng
Pan Li
Yang Zhou
Yuting Cao
Li Wan
Xun Guo
Xiaohong Lin
Rui Tang
Hongye He
Nianhong Wu
Qiaoqi Chen
Yaqin Hu
Xialin Xiong
Faqi Li
author_facet Ying Zhou
Chen Cheng
Qi Wang
Min Zheng
Pan Li
Yang Zhou
Yuting Cao
Li Wan
Xun Guo
Xiaohong Lin
Rui Tang
Hongye He
Nianhong Wu
Qiaoqi Chen
Yaqin Hu
Xialin Xiong
Faqi Li
author_sort Ying Zhou
collection DOAJ
description Background High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment.Methods M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy.Results Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU’s killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+ T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed.Conclusions Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host’s antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.
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spelling doaj-art-9227d2a674474077b999f1757a24530f2025-01-29T12:25:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-006226Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapyYing Zhou0Chen Cheng1Qi Wang2Min Zheng3Pan Li4Yang Zhou5Yuting Cao6Li Wan7Xun Guo8Xiaohong Lin9Rui Tang10Hongye He11Nianhong Wu12Qiaoqi Chen13Yaqin Hu14Xialin Xiong15Faqi Li162 The Affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China1 Department of Neurology, Peking University First Hospital, Beijing, ChinaNaval Medical University, Shanghai, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China2 Teaching and Research Section of Clinical Nursing, Xiangya Hospital Central South University, Changsha, Hunan, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaInstitute of Ultrasound Imaging of Chongqing Medical University, Chongqing, ChinaInnomodels Biotechnology (Beijing) Co., Ltd, Beijing, ChinaInstitute of Ultrasound Imaging of Chongqing Medical University, Chongqing, China1 Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USAInstitute of Ultrasound Imaging of Chongqing Medical University, Chongqing, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaBackground High-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment.Methods M@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy.Results Guided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU’s killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+ T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed.Conclusions Our findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host’s antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.https://jitc.bmj.com/content/11/1/e006226.full
spellingShingle Ying Zhou
Chen Cheng
Qi Wang
Min Zheng
Pan Li
Yang Zhou
Yuting Cao
Li Wan
Xun Guo
Xiaohong Lin
Rui Tang
Hongye He
Nianhong Wu
Qiaoqi Chen
Yaqin Hu
Xialin Xiong
Faqi Li
Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
Journal for ImmunoTherapy of Cancer
title Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
title_full Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
title_fullStr Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
title_full_unstemmed Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
title_short Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy
title_sort novel combination strategy of high intensity focused ultrasound hifu and checkpoint blockade boosted by bioinspired and oxygen supplied nanoprobe for multimodal imaging guided cancer therapy
url https://jitc.bmj.com/content/11/1/e006226.full
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