Transferrin-modified bone marrow mesenchymal stem cell co-loaded with phthalocyanine and perfluorohexane for targeted...

The advancement of cell-based drug delivery systems (Cell-DDS) enables precise tumor targeting. Utilizing bone marrow mesenchymal stem cells (BMSC) as carriers, transferrin (Tf)-modified BMSC (BMSC_Tf) were engineered via sugar metabolism replacement and click chemistry. Liposomes co-encapsulating phthalocyanine (Pc) and oxygen-carrying perfluorohexane (PFH) were integrated with BMSC_Tf through membrane fusion, constructing the Tf-functionalized delivery system Pc/O₂@BMSC_Tf. This system achieved Pc loading efficiency of 1.7 μg per 10⁵ cells and an oxygen-carrying capacity of 11.2 μg per 10⁷ cells, demonstrating active tumor targeting, significant antitumor efficacy in vitro and in vivo, and high biocompatibility. At tumor sites, localized near-infrared irradiation triggered Pc-mediated ROS generation, while the nanoliposomes provided real-time oxygen replenishment, overcoming hypoxia to potentiate photodynamic therapy (PDT). This novel stem cell-based drug delivery system represents a promising strategy for targeted tumor therapy.