Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects.
Short (14-20-mer range) synthetic oligodeoxynucleotides (ODNs) allow specific modulation of cellular gene expression at various stages, thus providing a versatile tool for fundamental studies and a rational approach to anticancer chemotherapy. However, several problems, such as metabolic stability, efficient cell internalization of ODNs and their efficient entrapment into liposomes continue to markedly limit this approach. To improve the target specificity and biological activity of ODN, three different length of poly(L-lysine) (PLL) were conjugated to ODN and these conjugates were encapsulated in N-stearyllactobionamide (N-SLBA)-modified liposomes, N-SLBA is a ligand for the asialoglycoprotein receptor. Then, we investigated their effects on cell cycle and survivin protein levels of HepG2 cells. The results showed that the encapsulation efficiency was improved because the polycationic charges of PLL neutralized the polyanionic charges of ODN. Among them, PLL (M(W) 2000 and 10,000)-conjugated ODN encapsulated in N-SLBA liposomes induced apoptosis of HepG2 cells and highly inhibited survivin gene expression.
Wang
Siling
S
Department of Pharmaceutics and Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. silingwang@hotmail.com
Cheng
Lihua
L
Yu
Fengbo
F
Pan
Weisan
W
Zhang
Jinghai
J
D017209:Apoptosis; D045744:Cell Line, Tumor; D004187:Disaccharides / Q000737:chemistry*; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry*; D000077022:Survivin; D014162:Transfection / Q000379:methods
C107489:BIRC5 protein, human; D004187:Disaccharides; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins; C514083:N-stearyllactobionamide; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D013229:Stearic Acids; D000077022:Survivin; D011107:Polylysine