Polymer‐DNA Carriers Co‐Deliver Photosensitizer and siRNA for Light‐Promoted Gene Transfection and Hypoxia‐Relieved Photodynamic Therapy

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA‐interference gene regulation, which makes gene‐photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self‐assembled from polymer‐DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self‐assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA‐administrated therapy exhibits a significantly improved anti‐tumor efficacy owing to the highly efficient co‐delivery capability. Developing synthetic polymer‐DNA molecular chimeras provides new opportunities for material development. Herein, we demonstrate that the micellar nanostructures self‐assembled from polymer‐DNA chimeras can efficiently, straightforwardly, and bio‐compatibly co‐deliver siRNA and organic photosensitizers, resulting in significantly enhanced gene/photodynamic synergistic anti‐tumor efficacy.