To date, we have explored the potential of various stimuli-responsive nanomedicine, including inorganic nanoparticles and biopolymers, for the delivery of a wide range of therapeutic agents such as chemotherapeutics, genes, and the gas molecule. For preparing self-assembled nanostructures, we judiciously conjugated a self-assembly pair into different polymer backbones, achieving highly stable nanostructure formation. Various self-assembled pairs, including a host-guest interaction of paclitaxel (PTX)/cyclodextrin (CD) and base-specific interactions between the sense and antisense strands of siRNA, were chemically conjugated on each polymer backbone. Another strategy is to modulate the size and structure of the assembled structure using the sequence-specific hybridization and dehybridization of pH-sensitive functional DNA known as the i-motif. According to pH changes, the structure of functional DNA was transformed dynamically, leading to a release of the cargo, thus achieving the specific delivery of siRNA or an anticancer drug, doxorubicin (DOX). In this presentation, we reveal the design, construction, and operation of a functional DNA-decorated dynamic gold (Au) nanomachine as a therapeutic agent for triple combinatorial anti-cancer therapy. Taking advantage of the intrinsic optical properties of Au nanoparticles, which depend on their size, a cytosine rich i-motif sequence was employed for intracellular pH-sensitive duplex dissociation and subsequent aggregation of the DNA-Au nanomachine, enabling anti-cancer drug release and photothermal ablation upon irradiation with infrared light. Moreover, another functional DNA sequence, a G-quadruplex, was exploited for the stable loading and intracellular delivery of a photosensitizer to achieve effective photodynamic therapy under red light illumination. The G-quadruplex-assisted enhanced reactive oxygen species generation, pH-responsive dynamic aggregation behavior, consequent drug release, and the photothermal effect were investigated. Furthermore, the combinatorial chemo, photodynamic, and photothermal therapeutic effects of the functional DNA-decorated Au nanomachines were evaluated in vitro and in vivo using a triple negative breast cancer model

DNA-driven nanomachines for drug and nitric oxide delivery

2019 Fall National Meeting

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