Photosensitizer Decorated Red Blood Cells as an Ultrasensitive Light-Responsive Drug Delivery System

Red blood cells (RBCs) have been widely explored as a natural drug delivery system (DDS) owing to their inherent biocompatibility and large internal cavities to load various types of functional molecules. Herein, we uncover that a photosensitizer, chlorin e6 (Ce6), could be decorated into the membrane of RBCs upon simple mixing, without affecting the membrane integrity and stability in dark. Upon light irradiation with a rather low power density, the singlet oxygen generated by Ce6 would lead to rather efficient disruption of RBC membrane. With doxorubicin (DOX), a typical chemotherapy drug, as the model, we engineer a unique type of light-responsive RBC-based DDS by decorating Ce6 on the cell membrane and loading DOX inside cells. The light triggered cell membrane breakdown would thus trigger instant release of DOX, enabling light-controlled chemotherapy with great specificity. Beyond that our RBC system could also be utilized for loading of larger biomolecules such as enzymes, whose release as well as catalytic function is also controlled by light. Our work thus presents a unique type of biocompatible cell-based DDS that can be precisely controlled by mild external stimuli, promising not only for cancer therapy but also for other potential applications in biotechnologies.