title: Anti-MUC1 Aptamer/Negatively Charged Amino Acid Dendrimer Conjugates for Targeted Delivery to Human Lung Adenocarcinoma A549 Cells.
abstract: We previously developed a negatively charged amino acid dendrimer to address the safety concerns associated with the constituent unit of these systems, which resulted in the formation of a sixth-generation glutamic acid-modified dendritic poly(L-lysine) system (KG6E). The aim of this study was to develop a nanocarrier for targeted drug delivery into cancer cells. In this study, we have synthesized a conjugate material consisting of anti-mucin 1 (MUC1) aptamer (anti-MUC1 apt) and KG6E (anti-MUC1 apt/KG6E) for targeted drug delivery to human lung adenocarcinoma A549 cells, which express high levels of the MUC1. The anti-MUC1 apt/KG6E was efficiently internalized by the A549 cells and subsequently transported to the endosomal and lysosomal compartments. In contrast, the cellular association of the sequence scrambled aptamer/KG6E conjugate (scrambled apt/KG6E) was much lower than that of the anti-MUC1 apt/KG6E in A549 cells. These results suggest that our newly developed anti-MUC1 apt/KG6E can be internalized in A549 cells via a MUC1 recognition pathway.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Marie
authors.initials: M
authors.lastname: Masuda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Wassana
authors.initials: W
authors.lastname: Wijagkanalan
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Suga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fuchigami
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism*; D011107:Polylysine / Q000737:chemistry
chemical_list: D052157:Aptamers, Nucleotide; D050091:Dendrimers; C060192:MUC1 protein, human; D018396:Mucin-1; D011107:Polylysine; D018698:Glutamic Acid