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• W1996939713 startingPage "e107" @default.
• W1996939713 abstract "Treatment with doxorubicin (Dox) results in serious systemic toxicities that limit effectiveness for cancer treatment and cause long-term health issues for cancer patients. We identified a new DNA aptamer to prostate-specific membrane antigen (PSMA) using fixed sequences to promote Dox binding and developed dimeric aptamer complexes (DACs) for specific delivery of Dox to PSMA(+) cancer cells. DACs are stable under physiological conditions and are internalized specifically into PSMA(+) C4-2 cells with minimal uptake into PSMA-null PC3 cells. Cellular internalization of DAC was demonstrated by confocal microscopy and flow cytometry. Covalent modification of DAC with Dox (DAC-D) resulted in a complex with stoichiometry ~4:1. Dox was covalently bound in DAC-D using a reversible linker that promotes covalent attachment of Dox to genomic DNA following cell internalization. Dox was released from the DAC-D under physiological conditions with a half-life of 8 hours, sufficient for in vivo targeting. DAC-D was used to selectively deliver Dox to C4-2 cells with endosomal release and nuclear localization of Dox. DAC-D was selectively cytotoxic to C4-2 cells with similar cytotoxicity as the molar equivalent of free-Dox. In contrast, DAC-D displayed minimal cytotoxicity to PC3 cells, demonstrating the complex displays a high degree of selectivity for PSMA(+) cells. DAC-D displays specificity and stability features that may be useful for improved delivery of Dox selectively to malignant tissue in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e107; doi:10.1038/mtna.2013.37; published online 16 July 2013." @default.
• W1996939713 created "2016-06-24" @default.
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• W1996939713 date "2013-01-01" @default.
• W1996939713 modified "2023-10-01" @default.
• W1996939713 title "Dimeric DNA Aptamer Complexes for High-capacity–targeted Drug Delivery Using pH-sensitive Covalent Linkages" @default.
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• W1996939713 doi "https://doi.org/10.1038/mtna.2013.37" @default.
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