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Lactoferrin-decorated vs PEGylated zein nanospheres for combined aromatase inhibitor and herbal therapy of breast cancer

2018; Taylor & Francis; Volume: 15; Issue: 9 Linguagem: Inglês

10.1080/17425247.2018.1505858

1744-7593

Sarah A El-Lakany, Nazik A. Elgindy, Maged W. Helmy, Marwa M. Abu‐Serie, Ahmed O. Elzoghby,

Graphene and Nanomaterials Applications

Herein, we propose combined aromatase inhibitor and herbal therapy of breast cancer as a synergistic therapeutic modality.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.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.Overall, combined delivery of aromatase inhibitors and herbal drugs via tumor-targeted zein nanospheres could serve as a promising strategy for breast cancer therapy.