ALPPL2 Aptamer-Mediated Targeted Delivery of 5-Fluoro-2'-Deoxyuridine to Pancreatic Cancer.
Nucleoside analogues are the most promising drugs for the treatment of pancreatic cancer to date. However, their use is often limited due to toxic side effects. Aptamer-mediated targeted delivery of these drugs to cancer cells could maximize their effectiveness and concomitantly minimize the toxic side effects by reducing uptake into normal cells. Previously, we identified a pancreatic cancer-specific, nuclease-resistant RNA aptamer, SQ2, which binds to alkaline phosphatase placental-like 2 (ALPPL2), a putative biomarker for pancreatic cancer. In this study, we demonstrate that the aptamer can be internalized into pancreatic cancer cells and can thus be used for the targeted delivery of therapeutics. Using the aptamer as a ligand, we established that glycophosphatidylinositol-anchored ALPPL2 is internalized by the cells through clathrin-independent and caveolae-dependent or dynamin-mediated cell-type-dependent pathways. Finally, we show that SQ2 can deliver nucleoside drug 5-fluoro-2'-deoxyuridine specifically to ALPPL2-expressing pancreatic cancer cells, inhibiting cell proliferation.
1 Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University , Suwon, Korea.
Pooja
P
Dua
1 Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University , Suwon, Korea.
Sajeesh
S
S
2 Department of Medical Biotechnology, Dongguk University , Seoul, Korea.
Soyoun
S
Kim
1 Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University , Suwon, Korea.
Dong-ki
DK
Lee
D000469:Alkaline Phosphatase / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000378:metabolism*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D052156:SELEX Aptamer Technique
C576827:5-fluoro-2'-deoxyuridine; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D014408:Biomarkers, Tumor; D004337:Drug Carriers; D058851:GPI-Linked Proteins; D008024:Ligands; C548269:ALPG protein, human; D000469:Alkaline Phosphatase; D034281:Dynamins; D003857:Deoxyuridine