‘Nanotrain’ for targeted drug transport of cancer theranostics

ISSN 1743-5889 10.2217/NNM.13.130 © 2013 Future Medicine Ltd Nanomedicine (2013) 8(9), 1369–1371 1369 Chemotherapy drugs lack specificity and induce cytotoxicity in both cancerous and healthy cells, resulting in limited maximum tolerated doses and reduced therapeutic efficacy. Studies have shown the use of aptamers as specific recognition elements for targeted transport of chemotherapeutic drugs. Targeted drug transport strategies are based on aptamer–drug conjugates or aptamer–nanomaterial assemblies; however, several limitations exist, including inefficient preparation of aptamer–drug conjugates, limited drug payload capacity, poor biodegradability and the requirement of specific aptamers for drug loading. This paper presents aptamer-tethered DNA nanotrains (aptNTrs) as carriers for targeted drug transport in cancer therapy. An aptNTr is a self-assembled long linear nanostructure formed from two short DNA strands upon initiation by aptamers, with the capability for selective recognition of target cancer cells and high numbers of spatially addressable sites. This allows for high-capacity loading of therapeutic agents, resulting in reduced cost, increased maximum tolerated dose, reduced side effects and increased therapeutic efficacy in cancer therapy. In vivo accumulation of nanoparticles is prevented because of the intrinsic biodegradability of DNA. In this study, reduced side effects and anti-tumor efficacy of delivered drugs by aptNTrs was evaluated in vivo using a mouse xenograft tumor model. Drug fluorescence dequenching provides a realtime imaging and signaling mechanism for drug release at target cells. Some of the advantages of aptNTrs include easy DNA synthesis, high payload capacity and cost reduction due to the short DNA in aptNTrs. This platform is also applicable to RNA-based systems. Research Highlights