Improved delivery and antimetastatic effects of Stattic by self-assembled amphiphilic pendant-dendron copolymer micelles in breast cancer cell lines

Abstract

Stattic is a signaling pathway inhibitor that could potentially impede the progression of tumor metastasis. However, the pharmaceutical applications of Stattic are hampered by its poor water solubility. In this study, we explored the integration of Stattic within amphiphilic pendant-dendron copolymeric (P71D3) micelles to improve its water solubility and delivery towards tumor cells. The P71D3/Stattic micelles with a 1:1.2 (P71D3:Stattic) ratio optimized for subsequent studies were 164 nm in diameter with a drug loading percentage of 52% w/w. These P71D3/Stattic micelles demonstrated a higher drug release (32%) in acidic tumor conditions compared to neutral physiological conditions (14%). However, rapid and high Stattic release was observed when dialyzed against a simulated plasma solution containing 4% albumin. Interestingly, when the same Stattic-loaded micelles and 4% albumin solution were in direct contact, the albumin molecules bound to the surface of the micelles, forming a protein corona. P71D3/Stattic micelles were found to be 30- to 90-fold more potent and to decrease the effective antimotility concentration by 3- to 6-fold compared to free Stattic in metastatic human and murine mammary cancer cells. The P71D3/Stattic micelles effectively enhanced the potency of the drug as determined from the in vitro studies, suggesting the use of P71D3/Stattic micelles as a promising antimetastatic agent worthy of further study.