<scp>Quatramer™</scp> encapsulation of dual‐targeted <scp>PI3‐Kδ</scp>/<scp>HDAC6</scp> inhibitor, <scp>HSB</scp>‐510, suppresses growth of breast cancer

Multiple studies have shown that the progression of breast cancer depends on multiple signaling pathways, suggesting therapies with multitargeted anticancer agents will offer improved therapeutic benefits through synergistic effects in inhibiting growth. Dual-targeted inhibitors phosphoinositide 3-kinase (PI3-K) and histone deacetylase (HDAC) emerged as promising therapy candidates. However, poor aqueous solubility bioavailability limited their efficacy cancer. The present study investigates encapsulation a PI3-Kδ/HDAC6 dual inhibitor into hybrid block copolymers (polylactic acid-methoxy polyethylene glycol; polylactic acid-polyethylene glycol-polypropylene glycol-polyethylene glycol-polylactic acid) (HSB-510) delivery system to target PI3-Kδ HDAC6 pathways cells. prepared HSB-510 showed an average diameter 96 ± 3 nm, zeta potential −17 2 mV, PDI ˂0.1 slow sustained release profile nonphysiological buffer. In vitro demonstrated substantial growth inhibition cell lines, MDA-MB-468, SUM-149, MCF-7, Ehrlich ascites carcinoma (EAC) well downregulation phospho-AKT, phospho-ERK, c-Myc levels. Importantly, bi-weekly treatment Balb/c wild-type mice harboring EAC cells at dose 25 mg/kg resulted significant tumor inhibition. was without any effect body weights mice. These results demonstrate novel Quatramer represents approach for successful targeting potentially other types.