Albumin Nanoparticle of Paclitaxel (Abraxane) Decreases while Taxol Increases Breast Cancer Stem Cells in Treatment of Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) has a high rate of metastasis, which is associated with breast cancer stem-like cells (CSCs). Although Taxol (micelle formulation of paclitaxel) is the first line chemotherapy to treat TNBC, it increases CSCs in residual tumors. Abraxane, albumin nanoparticle of...

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Bibliographic Details
Published in:Molecular pharmaceutics 2020-07, Vol.17 (7), p.2275-2286
Main Authors: Yuan, Hebao, Guo, Hongwei, Luan, Xin, He, Miao, Li, Feng, Burnett, Joseph, Truchan, Nathan, Sun, Duxin
Format: Article
Language:English
Subjects:
Albumin-Bound Paclitaxel - administration & dosage
Albumin-Bound Paclitaxel - chemistry
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Cell Line, Tumor
Cell Survival - drug effects
Disease Models, Animal
Drug Delivery Systems - methods
Female
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Nanoparticles - chemistry
Neoplastic Stem Cells - drug effects
Treatment Outcome
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - metabolism
Triple Negative Breast Neoplasms - pathology
Tumor Burden - drug effects
Xenograft Model Antitumor Assays
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Summary:Triple-negative breast cancer (TNBC) has a high rate of metastasis, which is associated with breast cancer stem-like cells (CSCs). Although Taxol (micelle formulation of paclitaxel) is the first line chemotherapy to treat TNBC, it increases CSCs in residual tumors. Abraxane, albumin nanoparticle of paclitaxel, showed lower plasma concentration compared to Taxol in both human and animal models, but it is not clear why Abraxane showed superior efficacy to Taxol in treatment of metastatic breast cancer in humans. In this study, we intend to investigate if Abraxane eliminates CSCs for its better efficacy. The results showed that Abraxane showed similar cytotoxicity in SUM149 cells in comparison with Taxol. Although Abraxane showed 3- to 5-fold lower blood drug concentration compared to Taxol, it achieved similar tumor drug concentration and 10-fold higher tumor/plasma ratio in SUM149 xenograft NOD/SCID mouse model. In addition, Abraxane and Taxol showed similar efficacy to shrink the tumor size in orthotopic breast cancer NOD/SCID mouse model. However, Abraxane decreased breast CSCs frequency by 3- to 9-fold, while Taxol increased breast CSCs frequency in an orthotopic breast cancer NOD/SCID mouse model. Furthermore, Abraxane increased 3- to 15-fold intracellular uptake in both ALDH+ CSCs and differentiated ALDH– cells in comparison with Taxol, which provides a mechanism for Abraxane’s superior efficacy to eliminate CSCs in comparison with Taxol. Our data suggest albumin nanoparticle Abraxane may have a broad implication to enhance drug’s efficacy by eliminating breast cancer stem cells for treatment of metastatic diseases.
ISSN:1543-8384
1543-8392
DOI:10.1021/acs.molpharmaceut.9b01221