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Updated: Jun 17, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Phosphate Ion-Responsive and Calcium Peroxide-Based Nanomedicine for Bone-Targeted Treatment of Breast Cancer Bone
Dehui Fan1, Jing Li1, Luwei Li1
1State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Material Science, Hebei University, Baoding, 071002, China.
Abstract:
The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O2, while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808 nm laser source, the O2 and free photosensitizer produced 1O2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.
Insights
This study introduces a novel nanomedicine that simultaneously targets breast cancer bone metastasis, repairs bone, and eliminates tumors. This dual-action approach offers a promising new treatment strategy for bone metastases.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Oncology
Background:
- Breast cancer bone metastasis presents a significant clinical challenge due to the inability of current therapies to both inhibit tumor growth and repair bone damage.
- Osteolytic bone injuries at metastatic sites exacerbate the disease, creating a vicious cycle that current treatments struggle to break.
Purpose of the Study:
- To develop and evaluate a novel nanomedicine for treating breast cancer bone metastasis.
- To create a therapeutic agent capable of simultaneously blocking tumor progression and promoting bone repair in metastatic bone lesions.
Main Methods:
- Development of phosphate ion-responsive, calcium peroxide-based nanoparticles.
- Surface functionalization with zoledronic acid (bone-targeting agent) and loading with indocyanine green (photosensitizer).
- In vivo evaluation in a mouse model of breast cancer bone metastasis, including intravenous administration and laser irradiation.
Main Results:
- Nanoparticles efficiently accumulated at bone metastasis sites, reacting with phosphate ions to produce hydroxyapatite nanoaggregates and oxygen (O2).
- Hydroxyapatite promoted bone matrix remineralization and induced tumor cell apoptosis, while released indocyanine green, upon laser activation, generated singlet oxygen (1O2) for enhanced anti-tumor effects.
- The treatment effectively blocked osteolysis and promoted bone remineralization, disrupting the tumor-bone vicious cycle.
Conclusions:
- The developed nanomedicine demonstrates a novel, safe, and efficient approach for treating breast cancer bone metastasis.
- This dual-action strategy effectively targets tumor growth and bone destruction, offering a potential breakthrough in managing bone metastases.
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