Abstract
Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic form before administration. Based on the excellent hydrophilicity and programmability of DNA, now, a general strategy to construct a precise drug-containing DNA framework for cancer treatment is reported. In this novel drug delivery system, carbonethyl bromide-modified camptothecin (CPT) is employed to directly react with phosphorothioate (PS) modified DNAs, resulting in the formation of chemotherapeutics-grafted DNAs with a responsive disulfide linkage. By tuning the number and site of PS modifications on DNA strands, hydrophilicity of the obtained DNA-drug conjugates (DDCs) can be regulated to retain their aqueous solubility and capability of molecular recognition. Subsequently, programmable DNA nanotechnology enables the self-assembly of a precise drug-containing tetrahedral framework with stimuli-responsive feature and enhanced antitumor efficacy both in vitro and in vivo.
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