Chemo/Photoacoustic Dual Therapy with mRNA-Triggered DOX Release and Photoinduced Shockwave Based on a DNA-Gold Nanoplatform

A multifunctional nanoparticle based on gold nanorod (GNR), utilizing mRNA triggered chemo-drug release and near-infrared photoacoustic effect, is developed for a combined chemo-photoacoustic therapy. The constructed nanoparticle (GNR-DNA/FA:DOX) comprises three functional components: (i) GNR as the drug delivery platform and photoacoustic effect enhancer; (ii) toehold-possessed DNA dressed on the GNR to load doxorubicin (DOX) to implement a tumor cell specific chemotherapy; and (iii) folate acid (FA) modified on GNR to guide the nanoparticle to target tumor cells. The results show that, upon an effective and specific delivery of the nanoparticles to the tumor cells with overexpressed folate receptors, the cytotoxic DOX loaded on the GNR-DNA nanoplatform can be released through DNA displacement reaction in melanoma-associated antigen gene mRNA expressed cells. With 808 nm pulse laser irradiation, the photoacoustic effect of the GNR leads to a direct physical damage to the cells. The combined treatment of the two modalities can effectively destroy tumor cells and eradicate the tumors with two distinctively different and supplementing mechanisms. With the nanoparticle, photoacoustic imaging is successfully performed in situ to monitor the drug distribution and tumor morphology for therapeutical guidance. With further in-depth investigation, the proposed nanoparticle may provide an effective and safe alternative cancer treatment modality.