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A nanoscale drug delivery carrier using nucleic acid aptamers for extended release of therapeutic

We have synthesized, characterized, and optimized a novel nano drug-delivery carrier that utilizes the versatile properties of nucleic acid for programmable and on-demand drug release. The drug-delivery carrier consists of 15 nm gold nanoparticles (AuNPs) functionalized with drug binding DNA aptamers via single-stranded (ss) anchor DNA. The presence of anchor DNA makes the nanocarrier flexible to be reprogrammed with various aptamers. Under the optimum binding conditions (0.4 M NaCl and 4 μM DNA), a maximum of 101 ± 8 anchor DNA strands were conjugated per particle. On binding DNA-aptamer:drug complexes to AuNPs, a maximum of 35 neomycin molecules were bound per AuNP. Controlled and extended release of drug from the synthesized carrier was obtained by temperature and affinity modulations. Furthermore, for the first time, we demonstrated that neomycin could bind to DNA with very high affinity (Kd = 98.101 nM). This DNA-based nanocarrier, designed using the principles of molecular biology, is expected to impact a number of treatment strategies.From the Clinical EditorIn this basic science work, the authors demonstrate the feasibility of utilizing a novel nano drug-delivery carrier with the versatile properties of nucleic acid for programmable and on-demand drug release.Graphical AbstractThe nano drug-delivery carrier was constructed by conjugating drug-bound DNA aptamer to gold nanoparticle (AuNPs) via single stranded (ss) anchor DNA. The presence of anchor DNA makes the nanocarrier flexible to be reprogrammed with aptamers that either bind different drugs or display different affinities for the same drug. Various methods of conjugating aptamer and drug:aptamer complex to AuNPs were investigated to obtain maximum loading of the drug on AuNPs. A controlled and extended release of drug from the synthesized carrier was obtained by altering the binding of the drug to aptamer via temperature change. Furthermore, aptamer-drug binding affinity modulated release of drug at a constant temperature was achieved.Download : Download high-res image (185KB)Download : Download full-size image


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