Photodynamic therapy (PDT) has received wide attention in cancer treatment. PDT consists of three components: a photosensitizer (PS), light, and oxygen. PS is not toxic in the dark, but can be activated by light at specific wavelengths, producing reactive oxygen species including cytotoxic 1O2. One limitation of PDT, however, is its high dependence on oxygen which is a precious resource in vivo, especially for tumors of relatively large sizes. PDT can further potentiate hypoxia that impedes PDT efficacy. To address the issue, we developed a novel RBC-PDT technology which harnesses red blood cells (RBCs) as PS vehicles. RBCs have been extensively studied as a drug delivery system for their availability, inherent bio-compatibility, flexibility, high in vivo stability, and long systemic circulation; they however, have seldom been used for PDT-related applications. RBCs afford high PS loading rate and long circulation half-lives. In this project, we first encapsulated a potent ZnF16Pc into ferritin nanocages (60 wt%) and then conjugated the resulting PS-loaded ferritins onto the surface RBCs by biotin-streptavidin conjugation. It was shown that ~2 × 107 ZnF16Pc molecules can be loaded onto each RBC while not damaging it. More interestingly, we observed that the surface bound PS can benefit from O2 released from RBCs to constantly producing 1O2, even in hypoxic areas, which represents a unique advantage of the RBC-PDT in tumor treatment. When tested in U87-MG subcutaneous tumor models, RBC-PDT induced significantly improved tumor inhibition (63.66% on day 15) compared to treatment with PS-loaded ferritins (38.69%), while causing minimal toxicity to the skin and other major organs. Overall, RBC-PDT has shown great promise as a safe and efficient treatment method, and it holds great potential in clinical translation.

Red blood cell-mediated photodynamic therapy for improved cancer treatment

249th National Meeting (2015)

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