Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer

Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature. Conventional chemo-immunotherapy suffers from poor tumor targeting and systemic toxicity, necessitating advanced delivery systems for synergistic drug combinations. This study constructed a biomimetic nan...

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Main Authors: Xiaoman Xu, Yunmei Song, Mingli Li, Fengxi Liu, Huiwen Zhang, Jingxia Xu, Juwei Gao, Yanna Lv, Bo Zhang, Sanjay Garg
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425005824
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author Xiaoman Xu
Yunmei Song
Mingli Li
Fengxi Liu
Huiwen Zhang
Jingxia Xu
Juwei Gao
Yanna Lv
Bo Zhang
Sanjay Garg
author_facet Xiaoman Xu
Yunmei Song
Mingli Li
Fengxi Liu
Huiwen Zhang
Jingxia Xu
Juwei Gao
Yanna Lv
Bo Zhang
Sanjay Garg
author_sort Xiaoman Xu
collection DOAJ
description Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature. Conventional chemo-immunotherapy suffers from poor tumor targeting and systemic toxicity, necessitating advanced delivery systems for synergistic drug combinations. This study constructed a biomimetic nanodrug delivery system by coating nanomicelles with 4T1 tumor cell membranes. This strategy leverages the homologous targeting ability of tumor cell membranes to improve the accumulation of nanomicelles within TNBC tissues. The cytotoxic agent bortezomib (BTZ) and the immune modulator resiquimod (R848) were encapsulated individually and co-administered to investigate the synergistic chemo-immunotherapeutic efficacy in TNBC treatment. The biomimetic nanomicelles exhibited excellent biocompatibility and homologous targeting capacity, significantly enhancing drug delivery efficiency at the tumor site. In vitro studies demonstrated that biomimetic nanomicelles effectively induced tumor cell apoptosis, repolarized tumor-associated macrophages toward the M1 phenotype and promoted dendritic cell maturation. In vivo experiments further confirmed that the biomimetic nanomicelles markedly inhibited tumor growth and metastasis, enhanced antitumor immune responses, and exhibited strong synergy with BTZ to improve overall therapeutic outcomes in TNBC. This dual-action biomimetic nanomicelles delivery platform achieved efficient chemo-immunotherapeutic synergy and represents a promising strategy for targeted treatment of TNBC, with strong potential for clinical translation.
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spelling doaj-art-b51685027fbb441a8a8cdad729feacbb2025-08-20T03:24:04ZengElsevierMaterials Today Bio2590-00642025-08-013310201210.1016/j.mtbio.2025.102012Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancerXiaoman Xu0Yunmei Song1Mingli Li2Fengxi Liu3Huiwen Zhang4Jingxia Xu5Juwei Gao6Yanna Lv7Bo Zhang8Sanjay Garg9School of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR China; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, AustraliaSchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, AustraliaSchool of Life Science and Engineering, Jining University, Qufu City, 273155, Shandong Province, PR ChinaDepartment of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, Shandong Province, PR ChinaSchool of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR ChinaSchool of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR ChinaSchool of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR ChinaSchool of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR China; Corresponding author.School of Pharmacy, Shandong Second Medical University, Weifang, 261053, Shandong Province, PR China; School of Life Science and Engineering, Jining University, Qufu City, 273155, Shandong Province, PR China; Corresponding author. School of Life Science and Engineering, Jining University, Qufu City, 273155, Shandong Province, PR China.School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, AustraliaTriple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature. Conventional chemo-immunotherapy suffers from poor tumor targeting and systemic toxicity, necessitating advanced delivery systems for synergistic drug combinations. This study constructed a biomimetic nanodrug delivery system by coating nanomicelles with 4T1 tumor cell membranes. This strategy leverages the homologous targeting ability of tumor cell membranes to improve the accumulation of nanomicelles within TNBC tissues. The cytotoxic agent bortezomib (BTZ) and the immune modulator resiquimod (R848) were encapsulated individually and co-administered to investigate the synergistic chemo-immunotherapeutic efficacy in TNBC treatment. The biomimetic nanomicelles exhibited excellent biocompatibility and homologous targeting capacity, significantly enhancing drug delivery efficiency at the tumor site. In vitro studies demonstrated that biomimetic nanomicelles effectively induced tumor cell apoptosis, repolarized tumor-associated macrophages toward the M1 phenotype and promoted dendritic cell maturation. In vivo experiments further confirmed that the biomimetic nanomicelles markedly inhibited tumor growth and metastasis, enhanced antitumor immune responses, and exhibited strong synergy with BTZ to improve overall therapeutic outcomes in TNBC. This dual-action biomimetic nanomicelles delivery platform achieved efficient chemo-immunotherapeutic synergy and represents a promising strategy for targeted treatment of TNBC, with strong potential for clinical translation.http://www.sciencedirect.com/science/article/pii/S2590006425005824Biomimetic nanomicellesHomologous targetingChemo-immune combination therapyTriple-negative breast cancer
spellingShingle Xiaoman Xu
Yunmei Song
Mingli Li
Fengxi Liu
Huiwen Zhang
Jingxia Xu
Juwei Gao
Yanna Lv
Bo Zhang
Sanjay Garg
Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
Materials Today Bio
Biomimetic nanomicelles
Homologous targeting
Chemo-immune combination therapy
Triple-negative breast cancer
title Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
title_full Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
title_fullStr Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
title_full_unstemmed Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
title_short Biomimetic tumor cell membrane-camouflaged nanomicelles for synergistic chemo-immunotherapy of Triple-negative breast cancer
title_sort biomimetic tumor cell membrane camouflaged nanomicelles for synergistic chemo immunotherapy of triple negative breast cancer
topic Biomimetic nanomicelles
Homologous targeting
Chemo-immune combination therapy
Triple-negative breast cancer
url http://www.sciencedirect.com/science/article/pii/S2590006425005824
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