Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy

Immune checkpoint blockade (ICB) therapy is a promising treatment that has shown significant effects in certain refractory and advanced cancers. However, not all patients respond to ICB therapy. The tumor microenvironment (TME) helps tumors evade immune surveillance and attack, contributing to the l...

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Main Authors: Qin Zhang, Ci Yin, Junjie Liu, Hua Yang, Yanping Zhang, Qiaoxi Qin, Nianhong Wu, Rui Tang, Yuting Cao, Min Zheng, Hongye He, Hongmei Dong, Yang Zhou, Jianli Ren, Zhengju Ren, Pan Li
Format: Article
Language:English
Published: Wiley-VCH 2025-04-01
Series:Small Structures
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Online Access:https://doi.org/10.1002/sstr.202400441
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author Qin Zhang
Ci Yin
Junjie Liu
Hua Yang
Yanping Zhang
Qiaoxi Qin
Nianhong Wu
Rui Tang
Yuting Cao
Min Zheng
Hongye He
Hongmei Dong
Yang Zhou
Jianli Ren
Zhengju Ren
Pan Li
author_facet Qin Zhang
Ci Yin
Junjie Liu
Hua Yang
Yanping Zhang
Qiaoxi Qin
Nianhong Wu
Rui Tang
Yuting Cao
Min Zheng
Hongye He
Hongmei Dong
Yang Zhou
Jianli Ren
Zhengju Ren
Pan Li
author_sort Qin Zhang
collection DOAJ
description Immune checkpoint blockade (ICB) therapy is a promising treatment that has shown significant effects in certain refractory and advanced cancers. However, not all patients respond to ICB therapy. The tumor microenvironment (TME) helps tumors evade immune surveillance and attack, contributing to the low response rate to ICB therapy. M1 macrophages primarily exert antitumor effects within the TME, whereas M2 macrophages support tumor growth and immune evasion through various mechanisms, making them a crucial component of the TME. To reduce M2 macrophages, mitigate TME, and ultimately enhance ICB therapy, perfluoropentane (PFP) is used as the phase‐change material and hematoporphyrin monomethyl ether is incorporated into the nanodroplets (NDs). With mannose modification on their surface, these NDs can effectively target M2 macrophages, denoted as MPH@NDs. When exposed to low‐intensity focused ultrasound, MPH@NDs cause mechanical injury and produce reactive oxygen species. This will lead to remodeling of the distribution of macrophages in the TME, transforming it into a proinflammatory microenvironment. This enhances cytotoxic T lymphocytes accumulation in tumors, remodels TME, and improves PD‐L1 immunotherapy efficacy. MPH@NDs demonstrate promising potential in remodeling the TME, enhancing ICB therapy, and suppressing tumor growth and distant metastasis.
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series Small Structures
spelling doaj-art-865d4cc5a67a4b048ab0b55d2d8eff042025-08-20T02:11:34ZengWiley-VCHSmall Structures2688-40622025-04-0164n/an/a10.1002/sstr.202400441Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade TherapyQin Zhang0Ci Yin1Junjie Liu2Hua Yang3Yanping Zhang4Qiaoxi Qin5Nianhong Wu6Rui Tang7Yuting Cao8Min Zheng9Hongye He10Hongmei Dong11Yang Zhou12Jianli Ren13Zhengju Ren14Pan Li15Department of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaUltrasound Medical Center Lanzhou University Second Hospital Cuiyingmen No. 82 Chengguan District Lanzhou 730030 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology Chongqing Traditional Chinese Medicine Hospital Chongqing 400021 ChinaDepartment of Imaging teaching and Research Chongqing College of Traditional Chinese Medicine Chongqing 402760 ChinaDepartment of Ultrasound The Third People's Hospital of Chengdu The Affiliated Hospital of Southwest Jiaotong University Chengdu 610031 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound Women and Children's Hospital of Chongqing Medical University Chongqing 400000 ChinaDepartment of Ultrasound, The Third People's Hospital of Chengdu The Affiliated Hospital of SouthwestJiaotong University Chengdu 610031 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Urology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaImmune checkpoint blockade (ICB) therapy is a promising treatment that has shown significant effects in certain refractory and advanced cancers. However, not all patients respond to ICB therapy. The tumor microenvironment (TME) helps tumors evade immune surveillance and attack, contributing to the low response rate to ICB therapy. M1 macrophages primarily exert antitumor effects within the TME, whereas M2 macrophages support tumor growth and immune evasion through various mechanisms, making them a crucial component of the TME. To reduce M2 macrophages, mitigate TME, and ultimately enhance ICB therapy, perfluoropentane (PFP) is used as the phase‐change material and hematoporphyrin monomethyl ether is incorporated into the nanodroplets (NDs). With mannose modification on their surface, these NDs can effectively target M2 macrophages, denoted as MPH@NDs. When exposed to low‐intensity focused ultrasound, MPH@NDs cause mechanical injury and produce reactive oxygen species. This will lead to remodeling of the distribution of macrophages in the TME, transforming it into a proinflammatory microenvironment. This enhances cytotoxic T lymphocytes accumulation in tumors, remodels TME, and improves PD‐L1 immunotherapy efficacy. MPH@NDs demonstrate promising potential in remodeling the TME, enhancing ICB therapy, and suppressing tumor growth and distant metastasis.https://doi.org/10.1002/sstr.202400441immune checkpoint blocking therapylow‐intensity focused ultrasoundnanodropletstumor microenvironmenttumor‐associated macrophages
spellingShingle Qin Zhang
Ci Yin
Junjie Liu
Hua Yang
Yanping Zhang
Qiaoxi Qin
Nianhong Wu
Rui Tang
Yuting Cao
Min Zheng
Hongye He
Hongmei Dong
Yang Zhou
Jianli Ren
Zhengju Ren
Pan Li
Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
Small Structures
immune checkpoint blocking therapy
low‐intensity focused ultrasound
nanodroplets
tumor microenvironment
tumor‐associated macrophages
title Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
title_full Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
title_fullStr Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
title_full_unstemmed Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
title_short Low‐Intensity Focused Ultrasound‐Responsive, Phase‐Change Nanodroplets to Remodel Macrophage Polarization and Enhance PD‐L1 Blockade Therapy
title_sort low intensity focused ultrasound responsive phase change nanodroplets to remodel macrophage polarization and enhance pd l1 blockade therapy
topic immune checkpoint blocking therapy
low‐intensity focused ultrasound
nanodroplets
tumor microenvironment
tumor‐associated macrophages
url https://doi.org/10.1002/sstr.202400441
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