DNA-Based pH-Responsive Core-Shell Drug Nanocarrier for Tumor-Targeted Chemo-Photodynamic Therapy

Developing highly efficient and nontoxic drug carriers, which can work well for both chemotherapy drugs and photosensitizers, is an urgent demand to improve the efficacy of chemo-photodynamic therapy and to promote its clinical applications. In this paper, a facile way is proposed to construct a DNA-based nanocarrier, to achieve the synergetic loading and delivery of doxorubicine (Dox) and porphyrin/G-quadruplex composited photosensitizer. The nanocarrier contains a gold nanoparticle (AuNP) core and a DNA layer. It is prepared via a nontemplated extension of short DNA primers on AuNP core through terminal deoxynucleotidyl transferase catalysis and subsequent DNA hybridization. Through the intercalation of Dox in duplex DNA and the forming of porphyrin/G-quadruplex complex, the drugs responsible for chemotherapy and photodynamic therapy are efficiently loaded in the nanocarrier, and then delivered to and accumulated at tumor sites. Inside tumor cells, i-motif may form under acidic conditions, thus triggering pH-responsive payload release, and making the drug concentration achieving the therapeutic limitation in a short time. Highly efficient drug delivery and antitumor performance of the nanocarrier system are well demonstrated by both in vitro and in vivo experiments. The proposed nanocarrier may be developed as a promising tool for clinical drug delivery and disease therapy.