Co-delivery of anti-vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression
Journal
Journal of Biomedical Materials Research - Part A
Journal Volume
97 A
Journal Issue
3
Pages
330-338
Date Issued
2011
Author(s)
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. ? 2011 Wiley Periodicals, Inc.
Subjects
doxorubicin; micelle; polyethylenimine; siRNA; stearic acid
SDGs
Other Subjects
Amphiphilic structure; Anti-tumors; Anti-vascular endothelial growth factors; Binding efficiency; Cationic charges; Cellular uptake efficiency; Doxorubicin; Gene carrier; Gene Delivery; Hydrophilic shell; Hydrophobic core; Hydrophobic drug; Model study; Nanomicelles; Nonviral; polyethylenimine; Polyethylenimines; Polymeric micelle; Polyplexes; Positive surface charge; Post-transcriptional gene silencing; Serum proteins; siRNA; Tumor growth; Vascular endothelial growth factor; Viral vectors; Biodegradable polymers; Chemotherapy; Drug interactions; Efficiency; Gene therapy; Gene transfer; Hydrophobicity; Peptides; Stearic acid; Tumors; Micelles; doxorubicin; nanoparticle; polyethyleneimine; small interfering RNA; stearic acid; vasculotropin; animal experiment; animal model; antineoplastic activity; article; binding affinity; cancer inhibition; cytotoxicity; drug delivery system; drug formulation; drug stability; drug uptake; gene silencing; gene targeting; human; human cell; liver cell carcinoma; male; micelle; mouse; nonhuman; physical chemistry; posttranscriptional gene silencing; RNA binding; Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Doxorubicin; Drug Carriers; Gene Silencing; Humans; Male; Mice; Mice, SCID; Micelles; Neoplasms; Polyethyleneimine; RNA, Small Interfering; Stearic Acids; Vascular Endothelial Growth Factor A
Type
journal article