Selective delivery of an anticancer drug with aptamer-functionalized liposomes to breast cancer cells in vitro and in vivo

Selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. To address this need, DNA aptamers have attracted significant attention as possible targeting ligands. However, while their use in targeting cancer cells has been reported, their effectiveness has rarely been est...

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Published inJournal of materials chemistry. B, Materials for biology and medicine Vol. 1; no. 39; pp. 5288 - 5297
Main Authors Xing, Hang, Tang, Li, Yang, Xujuan, Hwang, Kevin, Wang, Wendan, Yin, Qian, Wong, Ngo Yin, Dobrucki, Lawrence W., Yasui, Norio, Katzenellenbogen, John A., Helferich, William G., Cheng, Jianjun, Lu, Yi
Format Journal Article
LanguageEnglish
Published England 21.10.2013
Subjects
binding capacity
Breast
breast neoplasms
Cancer
chemistry
cytotoxicity
DNA
Doxorubicin
Drug delivery systems
drug therapy
human cell lines
In vitro testing
ligands
Liposomes
mice
neoplasm cells
nucleotide aptamers
Surgical implants
Tumors
breast cancer
targeted drug delivery
cancer targeting
DNA aptamer
liposome
nucleolin
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Summary:Selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. To address this need, DNA aptamers have attracted significant attention as possible targeting ligands. However, while their use in targeting cancer cells has been reported, their effectiveness has rarely been established . Here we report the development of a liposomal drug delivery system for targeted anticancer chemotherapy. Liposomes were prepared containing doxorubicin as a payload, and functionalized with AS1411, a DNA aptamer with strong binding affinity for nucleolin. AS1411 aptamer-functionalized liposomes increased cellular internalization and cytotoxicity to MCF-7 breast cancer cells as compared to non-targeting liposomes. Furthermore, targeted liposomal doxorubicin improved antitumor efficacy against xenograft MCF-7 breast tumors in athymic nude mice, attributable to their enhanced tumor tissue penetration. This study suggests that AS1411 aptamer-functionalized liposomes can recognize nucleolin overexpressed on MCF-7 cell surface, and therefore enable drug delivery with high specificity and selectivity.
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These authors contributed equally to this work.
ISSN:2050-750X
2050-7518
2050-7518
DOI:10.1039/c3tb20412j