Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis

Bone metastasis is a fatal consequence of breast cancer that occurs when patients fail to respond to conventional therapies and mainly result from a vicious cycle involving dysregulated bone homeostasis and uncontrolled tumor growth. Recent research has underscored the significance of Siglec-15, a m...

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Main Authors: Chengkuan Liu, Yangui Zhong, Haibo Huang, Siyuan Lan, Jing Li, Deqiu Huang, Wen Zhang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S259000642400423X
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author Chengkuan Liu
Yangui Zhong
Haibo Huang
Siyuan Lan
Jing Li
Deqiu Huang
Wen Zhang
author_facet Chengkuan Liu
Yangui Zhong
Haibo Huang
Siyuan Lan
Jing Li
Deqiu Huang
Wen Zhang
author_sort Chengkuan Liu
collection DOAJ
description Bone metastasis is a fatal consequence of breast cancer that occurs when patients fail to respond to conventional therapies and mainly result from a vicious cycle involving dysregulated bone homeostasis and uncontrolled tumor growth. Recent research has underscored the significance of Siglec-15, a membrane protein implicated in immunosuppression and osteoclast generation. Targeting Siglec-15 may disrupt the “vicious cycle” that causes bone metastases in patients with breast cancer. Herein, we explored the efficacy of targeting Siglec-15 in conjunction with photothermal chemotherapy to impede the progression of bone metastatic during breast cancer and repair tumor-induced osteolysis. First, we formulated an injectable photothermal bioactive glass (BG)-based hydrogel for the local delivery of Siglec-15 shRNA and doxorubicin. The results demonstrated that the hydrogel could kill tumor cells directly through photothermal chemotherapy, provoke intense immune responses and improve the local immunosuppressive microenvironment, which could effectively prevent tumor metastasis and recurrence in a murine model. The combined effect of BGs and Siglec15 shRNA can normalize dysregulated bone homeostasis at the bone metastasis site and significantly reduced bone destruction. Overall, the use of Siglec-15-targeting integrated BG hydrogels may provide a promising therapeutic strategy for treating bone metastasis caused by breast cancer.
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spelling doaj-art-b335412e4b234f0a9c78b97d050d87fb2025-08-20T02:37:39ZengElsevierMaterials Today Bio2590-00642024-12-012910136210.1016/j.mtbio.2024.101362Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasisChengkuan Liu0Yangui Zhong1Haibo Huang2Siyuan Lan3Jing Li4Deqiu Huang5Wen Zhang6Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR ChinaResearch Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR ChinaSecond People's Hospital of Shenzhen, Shenzhen, Guangdong, PR ChinaSchool of Medical Information Engineering, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Intelligent Chinese Medicine Research Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Corresponding author. School of Medical Information Engineering, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China.Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China; Corresponding author. Research Centre of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, PR China.Bone metastasis is a fatal consequence of breast cancer that occurs when patients fail to respond to conventional therapies and mainly result from a vicious cycle involving dysregulated bone homeostasis and uncontrolled tumor growth. Recent research has underscored the significance of Siglec-15, a membrane protein implicated in immunosuppression and osteoclast generation. Targeting Siglec-15 may disrupt the “vicious cycle” that causes bone metastases in patients with breast cancer. Herein, we explored the efficacy of targeting Siglec-15 in conjunction with photothermal chemotherapy to impede the progression of bone metastatic during breast cancer and repair tumor-induced osteolysis. First, we formulated an injectable photothermal bioactive glass (BG)-based hydrogel for the local delivery of Siglec-15 shRNA and doxorubicin. The results demonstrated that the hydrogel could kill tumor cells directly through photothermal chemotherapy, provoke intense immune responses and improve the local immunosuppressive microenvironment, which could effectively prevent tumor metastasis and recurrence in a murine model. The combined effect of BGs and Siglec15 shRNA can normalize dysregulated bone homeostasis at the bone metastasis site and significantly reduced bone destruction. Overall, the use of Siglec-15-targeting integrated BG hydrogels may provide a promising therapeutic strategy for treating bone metastasis caused by breast cancer.http://www.sciencedirect.com/science/article/pii/S259000642400423XBioactive glassSiglec-15Photothermal chemotherapyBone metastasis
spellingShingle Chengkuan Liu
Yangui Zhong
Haibo Huang
Siyuan Lan
Jing Li
Deqiu Huang
Wen Zhang
Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
Materials Today Bio
Bioactive glass
Siglec-15
Photothermal chemotherapy
Bone metastasis
title Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
title_full Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
title_fullStr Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
title_full_unstemmed Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
title_short Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
title_sort killing two birds with one stone siglec 15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis
topic Bioactive glass
Siglec-15
Photothermal chemotherapy
Bone metastasis
url http://www.sciencedirect.com/science/article/pii/S259000642400423X
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