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In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer

Cited 74 time in Web of Science Cited 77 time in Scopus

Li, Xingshu; Jeon, Yun-Hui; Kwon, Nahyun; Park, Jun-Gyu; Guo, Tian; Kim, Hang-Rae; Huang, Jian-Dong; Lee, Dong-Sup; Yoon, Juyoung

Issue Date
Pergamon Press Ltd.
Biomaterials, Vol.266, p. 120430
Immunogenic photodynamic therapy (PDT) has the potential to moderate the shortfalls of cancer immunotherapy. However, its efficacy is severely limited particularly because of the lack of optimal photosensitizers and smart delivery processes and the inherent shortcomings of PDT (e.g., hypoxia resistance). Here, we demonstrate a clinically promising approach that utilizes a water-soluble phthalocyanine derivative (PcN4) concomitantly delivered with a hypoxia-activated prodrug (AQ4N) to amplify the effect of PDT and enhance cancer immunotherapy. After intravenous injection, PcN4 selectively interacted with endogenous albumin dimers and formed supramolecular complexes, providing a facile and green approach for tumor-targeted PDT. The concomitant delivery of AQ4N overcame the limitations of hypoxia in PDT and improved the antitumor activity of PDT. Treatment with PcN4-mediated and AQ4N-amplified PDT almost completely eradicated sizable primary tumors in a triple-negative breast cancer model and significantly activated CD8(+) T cells. As the majority of tumor infiltrating CD8(+) T cells were both PD-1- and TIM3-positive, additional combination therapy using PD-L1/PD-1 pathway blockade was warranted. After combination with immune checkpoint blockade treatment, an enhanced abscopal effect was achieved in both distant and metastatic tumors.
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  • College of Medicine
Research Area Function, Immune modulation by metabolites, T-cell anergy, differentiation of memory CD8+ T cells, metabolism


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