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

Abstract

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 in vitro has been reported, their effectiveness has rarely been established in vivo. 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.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

“…15,16 In contrast with previously reported RNA aptamers, DNA aptamers have shown reduced susceptibility to biodegradation, which makes them more favorable for clinical applications. 3,4 In order to develop a convenient and sensitive diagnostic assay for cancer by detecting TN-C protein, we evaluated GBI-10 aptamer as a targeted drug delivery system in this study.…”

“…Using peptides and antibodies (Abs) as targeting ligands against different cell-surface receptors is one of the most common approaches to achieve this goal. 3,4 Recently, nucleic acid-based aptamers have made an important impact on biomedical application, especially as new targeting ligands in the aspect of targeting cancers. [5][6][7][8] Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) obtained by an in vitro process called systematic evolution of ligands by exponential enrichment (SELEX).…”

“…3,4,[10][11][12][13] In 2004, FDA-approved Macugen (pegaptanib) as an antiangiogenic therapeutic agent for neovascular (wet) age-related macular degeneration. In addition, a variety of other aptamers, such as AS1411, are currently under clinical trials.…”

“…Despite promising in vitro studies, few studies of DNA aptamer nanomedicine constructs have shown successful efficacy in vivo. 3 Thus, in this initial study, experiments were conducted at 4°C to prove the initial targeting possibility of the GBI-10 targeted MRI CA to TN-C in tumor cells.…”

“…They are generally considered nonimmunogenic and biocompatible, much more stable to heat, pH, and organic solvents, easier to prepare and scale up, and with smaller molecular weight (8)(9)(10)(11)(12)(13)(14)(15). 3,8 The ssDNA or ssRNA can fold into welldefined 3D-structures and bind to their target with high affinity (μM-pM range) and specificity. 10 Furthermore, aptamers can be chemically modified to enhance their stability and affinity with targets.…”