Multifunctional\nDNA Polymer-Assisted Upconversion Therapeutic Nanoplatform for Enhanced\nPhotodynamic Therapy

Abstract

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