Aptamer-guided DNA tetrahedrons as a photo-responsive drug delivery system for Mucin 1-expressing breast cancer cells

Abstract Photosensitizers are crucial for photodynamic therapy. However, conventional photosensitizers have poor selectivity, and their targeted delivery by nanocarriers has become a major research focus. The aim of this study was to construct a targeted delivery system for new photosensitizers using aptamer-guided DNA tetrahedra. Mucin 1 protein is overexpressed in some cancer cells. The sequence of a Mucin 1 aptamer (MUC1) was linked to a DNA tetrahedron to form MUC1 aptamer-modified tetrahedral nanostructures (MUC1-TDNs) for the selective targeting of MUC1-positive tumor cells. The photosensitizer, TMPyP4, was loaded into MUC1-TDNs owing to the high affinity of TMPyP4 for DNA; consequently, a targeted photosensitizer delivery system (MUC1-TDNs-TMPyP4, MTT) was obtained. This system allowed for the selective delivery of TMPyP4 to MUC1-positive cancer cells. Moreover, MTT promoted the production of reactive oxygen species as well as cytotoxicity in MUC1-positive cells, while less killing effect were observed in MUC1-negative cells. We designed a MUC1-targeted delivery system of photosensitizers based on DNA tetrahedron, thus providing a new approach for the targeted release of photosensitizers.