Multifunctional DNA Polymer-Assisted Upconversion Therapeutic Nanoplatform for Enhanced Photodynamic Therapy

摘要

Although considerable clinical attempts on various kinds of cancers have been made, photodynamic therapy (PDT) still suffers from attenuated therapeutic effects because of the developed resistance of cancer cells. As a novel antiapoptosis protein, survivin has been demonstrated to be selectively overexpressed in a great number of human malignancies and plays a significant part in cancer progression and therapeutic resistance. Herein, we present an upconversion nanoplatform for enhanced PDT by DNAzyme-mediated gene silencing of survivin. In our system, a long single-stranded DNA (ssDNA) with a repetitive aptamer (AS1411) and survivin-targeted DNAzyme was fabricated by rolling circle amplification (RCA) and adsorbed on the upconversion nanoparticles (UCNPs) by electrostatic attraction. The multivalence of the ssDNA endows the upconversion nanoplatform with high recognition and loading capacity of photosensitizers and DNAzymes. When the nanoplatform is targeted internalized into cancer cells, PDT can be triggered by near-infrared (NIR) light to generate reactive oxygen species (ROS) for killing the cancer cells. Moreover, the encoded DNAzyme can efficiently inhibit the gene expression of survivin, providing the potential to enhance the efficiency of PDT. This study thus highlights the promise of an upconversion photodynamic nanoplatform for admirable combination therapy in cancer.