Decreased Lung Metastasis in Triple Negative Breast Cancer Following Locally Delivered Supratherapeutic Paclitaxel-Loaded Polyglycerol Carbonate Nanoparticle Therapy

Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, cu...

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Bibliographic Details
Published in:Biomacromolecules 2024-03, Vol.25 (3), p.1800-1809
Main Authors: Sabatelle, Robert C., Chu, Ngoc-Quynh, Blessing, William, Kharroubi, Hussein, Bressler, Eric, Tsai, Lillian, Shih, Angela, Grinstaff, Mark W., Colson, Yolonda
Format: Article
Language:English
Subjects:
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Female
Glycerol
Humans
Lung Neoplasms - drug therapy
Nanoparticles
Neoplasm Metastasis
Paclitaxel
Polymers
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - pathology
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Summary:Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, current treatments are insufficient for treating or preventing metastatic disease. Herein, we describe supratherapeutic paclitaxel-loaded nanoparticles (81 wt % paclitaxel) to treat the primary tumor and reduce the risk of subsequent metastatic lesions in the lungs. Primary tumor volume and lung metastasis are reduced by day 30, compared to the paclitaxel clinical standard treatment. The ultrahigh levels of paclitaxel afford an immunotherapeutic effect, increasing natural killer cell activation and decreasing NETosis in the lung, which limits the formation of metastatic lesions.
ISSN:1525-7797
1526-4602
1526-4602
DOI:10.1021/acs.biomac.3c01258