Programmable Biporphyrin‐G‐Quadruplex Nanoflowers for Simultaneous Tumor Cell Recognition and Enhanced Photodynamic Therapy

Abstract Oxygen‐based photodynamic therapy (PDT) is often hindered by the hypoxic conditions within the tumor microenvironment (TME). To overcome this challenge, multifunctional DNA nanoflowers is designed using rolling circle amplification (RCA), incorporating porphyrin and G‐quadruplex (G4) DNA to achieve both tumor cell recognition and enhanced PDT performance. The spatial arrangement of AS1411 aptamers and G4 motifs within the DNA nanoflowers increases the binding specificity to cancer cells, thereby facilitating targeted detection. Furthermore, the incorporation of hemin into the G4 complex endows the nanoflowers with peroxidase‐like catalytic activity, enabling colorimetric detection of tumor cells through endogenous hydrogen peroxide production. This catalytic process generates oxygen to alleviate hypoxia within the TME and amplifies the production of reactive oxygen species (ROS), thereby enhancing PDT effectiveness. Additionally, the multifunctional DNA nanoflowers induce both ferroptosis and apoptosis in cancer cells, effectively inhibiting the progression of triple‐negative breast cancer. In summary, these multifunctional DNA nanoflowers offer a promising and highly selective approach to enhancing cancer treatment outcomes.