title: Co-delivery of anti-vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression.
abstract: Nonviral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multifunctional nanomicelles for both drug and gene delivery application. Polyethylenimine (PEI) was modified by grafting stearic acid (SA) and further formulated to polymeric micelles (PEI-SA) with positive surface charge for gene delivery evaluation. Our results showed that PEI-SA micelles provided high siRNA binding efficiency and exhibited low cytotoxicity compared with unmodified PEI. siRNA delivered by PEI-SA carriers also demonstrated significantly higher cellular uptake efficiency and stability even in the presence of serum proteins when compared with free siRNA. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. In the animal intratumoral model study, the combination of co-delivering doxorubicin and vascular endothelial growth factor (VEGF) siRNA delivered by PEI-SA micelles showed a promising effect on anti-tumor growth. The amphiphilic structure of PEI-SA micelles provides advantages for multifunctional tasks; such that hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and hydrophobic core can serve as a payload for hydrophobic drugs, making it truly a promising multifunctional vehicle for both genetic and chemotherapy application.
authors.affiliation: Institute of Biomedical Engineering, College of Engineering, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Section 1, Taipei, Taiwan. yyhuang@ntu.edu.tw
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Huang
authors.forename: Wei-Ti
authors.initials: WT
authors.lastname: Kuo
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Chou
authors.forename: Yi-You
authors.initials: YY
authors.lastname: Huang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D013229:Stearic Acids / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D034741:RNA, Small Interfering; D013229:Stearic Acids; D042461:Vascular Endothelial Growth Factor A; C031183:stearic acid; D004317:Doxorubicin; D011094:Polyethyleneimine