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

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

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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.

Original languageEnglish
Article number120430
JournalBiomaterials
Volume266
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Juyoung Yoon thanks the National Research Foundation of Korea ( NRF ), which was funded by the Korea government ( MSIP ) (No. 2012R1A3A2048814 ). Dong-Sup Lee thanks the Basic Research Laboratory ( 2017R1A4A1015745 ) through the National Research Foundation of Korea ( NRF ) funded by the Korean Government (Ministry of Science & ICT ). Jian-Dong Huang thanks National Natural Science Foundation of China (Grant Nos. U1705282 ). Xingshu Li thanks National Natural Science Foundation of China (Grant Nos. 22078066 ). Jun-Gyu Park is grateful for the fellowship by the BK21 Plus Program.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Cancer immunotherapy
  • Hypoxia-activated prodrug
  • Photodynamic therapy
  • Phthalocyanine
  • Supramolecular self-assembly

Fingerprint

Dive into the research topics of 'In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer'. Together they form a unique fingerprint.

Cite this