Inhibition of Breast Cancer Metastasis by Pluronic Copolymers with Moderate Hydrophilic-Lipophilic Balance.

Abstract

Metastasis is the primary cause resulting in the high mortality of breast cancer. The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range of hydrophilic-lipophilic balance (HLB) including Pluronic L61, P85, P123, F127, F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The results indicated that P85 and P123 could strongly inhibit the migration and invasion of 4T1 cells. The effects of the polymers on cell healing, migration, and invasion exhibited bell-shaped dependencies on HLB of Pluronic copolymers, and the better antimetastasis effects of Pluronic copolymers could be achieved with the HLB between 8 and 16. P85 and P123 themselves could significantly inhibit pulmonary metastasis in 4T1 mammary tumor metastasis model in situ. In addition, a synergetic antimetastasis effect could be achieved during drug combination of doxorubicin hydrochloride (DOX) and P85 or P123 intravenously. The metastasis effects of P85 and P123 both in vitro and in vivo were partially attributed to the downregulation of matrix metalloproteinase-9 (MMP-9). Therefore, Pluronic copolymers with moderate HLB 8-16 such as P85 and P123 could be promising excipients with therapeutics in drug delivery systems to inhibit breast cancer metastasis.

• Authors: Huiping Sun, Qingshuo Meng, Shan Tang, Jinghan Su, Qi Yin, Lingli Chen, Wangwen Gu, Haijun Yu, Zhiwen Zhang, Siling Wang, Yaping Li
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 12 Issue 9 Pg. 3323-31 (Sep 08 2015) ISSN: 1543-8392 [Electronic] United States
• PMID: 26220770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excipients
• Micelles
• Polymers
• pluronic L61
• Poloxamer
• Matrix Metalloproteinase 9

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Cell Cycle
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Excipients
• Female
• Humans
• Hydrophobic and Hydrophilic Interactions
• Lung Neoplasms (drug therapy, enzymology, secondary)
• Matrix Metalloproteinase 9 (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Poloxamer (pharmacology)
• Polymers (pharmacology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays