Lactoferrin-decorated vs PEGylated zein nanospheres for combined aromatase inhibitor and herbal therapy of breast cancer.
Ключови думи
Резюме
OBJECTIVE
Herein, we propose combined aromatase inhibitor and herbal therapy of breast cancer as a synergistic therapeutic modality.
METHODS
Zein nanospheres were prepared by phase separation for co-delivery of exemestane and luteolin. To enhance their tumor-targeting capability, the nanospheres were coated with PEGylated phospholipids and lactoferrin for passive and active targeting, respectively.
RESULTS
The developed nanospheres demonstrated a small particle size and controlled drug release. In addition, the nanospheres revealed high serum stability, acceptable hemocompatibility, and good physical stability. Moreover, a 5-fold scale-up of zein nanospheres could be enabled followed by spray-drying using 2.5% mannitol as a drying adjuvant. PEGylated and lactoferrin-targeted nanospheres showed enhanced cytotoxicity against MCF-7 and 4T1 breast cancer cells with higher selectivity to cancer cells rather than normal fibroblasts. The in-vivo pharmacokinetics and anti-tumor efficacy confirmed the superiority of zein nanospheres particularly after PEGylation compared to free drug(s). The enhanced anti-cancer activity of nanocarriers was revealed as prolonged circulation half-life, lower % change in tumor volume, reduced expression of aromatase, Cyclin D1 and VEGF markers as well as amplified apoptosis and necrosis.
CONCLUSIONS
Overall, combined delivery of aromatase inhibitors and herbal drugs via tumor-targeted zein nanospheres could serve as a promising strategy for breast cancer therapy.