title: Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma.
abstract: Aim of the investigation was to develop folate-functionalized lipid nanoemulsion (LNE) comprising chemo-radiotherapeutics for targeted delivery to nasopharyngeal carcinoma (NPC). Soy lecithin nanoemulsion of doxorubicin (Dox) and yittrium-90 (90Y) was prepared by nanoprecipitation using ultrasonic homogenization technique followed by folic acid conjugation. Nanoemulsion (Dox-LNE) was characterized as positively charged (zeta potential), spherical shape (transmission electron microscopy) nano-droplets of uniform size distribution (polydispersity index). No significant variation in parameters such as particle size, zeta potential, and polydispersity index was observed when the stability of Dox-LNE was assessed during long-term storage at room temperature and at 8000 rpm, 121°C temperature, and 5000 time dilution in water. In vitro release of Dox from Dox-LNE was observed to be controlled for at least 48 h. Folate decoration over Dox-LNE surface (FD-Dox-LNE) and incorporation of 90Y in FD-Dox-LNE (FD-Dox + 90Y-LNE) changed droplet size up to 50 nm; however, surface charge of Dox-LNE did not change significantly. FD-Dox + 90Y-LNE inhibited growth of cancerous cell line like CNE1 (folate receptor rich) in vitro and alleviated tumor volume in NPC-induced nude mice significantly as compared to Dox + 90Y-LNE. Massive necrosis and hemorrhage of CNE1 cells were observed by FD-Dox + 90Y-LNE (89.9%); however, inhibition of growth of nasal epithelial cells (RPMI 2650; folate deficient) by FD-Dox + 90Y-LNE and Dox + 90Y-LNE was observed to be 21.5 and 43.65%, respectively. The investigation highlights the vast utility of folate-decorated lipid emulsion in delivering chemo-radiotherapeutics to the specific NPC site. FD-Dox + 90Y-LNE might offer a cost-effective, safe, efficacious, and clinically pertinent option to the available therapeutics.
authors: Department of Otolaryngology, Qilu Hospital of Shandong University, NO.107, Wenhua West Road, Jinan, 250012, Shandong Province, People's Republic of China.
authors: Ying
authors: Y
authors: Liu
authors: Department of Otolaryngology, Qingdao district of Qilu Hospital, Shandong University, Qingdao, China.
authors: Xue-Min
authors: XM
authors: Yu
authors: Department of Otolaryngology, Qingdao district of Qilu Hospital, Shandong University, Qingdao, China.
authors: Rui-Jie
authors: RJ
authors: Sun
authors: Department of Otolaryngology, Qilu Hospital of Shandong University, NO.107, Wenhua West Road, Jinan, 250012, Shandong Province, People's Republic of China. panxinliang452@hotmail.com.
authors: Xin-Liang
authors: XL
authors: Pan
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage; D004655:Emulsions; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*
chemical_list: D004655:Emulsions; D008055:Lipids; D004317:Doxorubicin; D005492:Folic Acid
keywords: chemo-radiotherapeutics; doxorubicin; folic acid; lipid nanoemulsion; nasopharyngeal carcinoma