A pH-responsive (PR) DNA system that can produce well-defined, pH-dependent conformational changes has been used to construct several functional DNA nanostructures and nanodevices.
Recently, we found this PR-DNA-gold nanoparticle (GNP) conjugate can be used for efficient pH-targeted delivery of chemotherapeutic drugs, such as doxorubicin, DOX.
The drug is bound stably at normal physiological pH (e.g. 7.4) and is only released as the environment becomes weakly acidic (e.g. pH 5.0) as is the case for many tumour cells.
Moreover, the PR-DNA-GNP nanocarrier has high uptake by model cancer cells with efficient pH-triggered intracellular drug release, leading to high cytotoxicity. PEGylation of the DNA-GNP nanocarrier effectively prevents non-specific adsorption of serum proteins and greatly increases its resistance to nuclease degradation.
Further, it can also efficiently deliver cell-membrane impermeable agents (e.g. propidium iodide, PI, and a Ru-based metal complex) to cancer cells and therefore appears to be a general, nanoscale delivery platform for any DNA-binding agent.