Journal
BIOMATERIALS
Volume 266, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120430
Keywords
Cancer immunotherapy; Photodynamic therapy; Phthalocyanine; Supramolecular self-assembly; Hypoxia-activated prodrug
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [2012R1A3A2048814]
- Basic Research Laboratory through the National Research Foundation of Korea (NRF) - Korean Government (Ministry of Science ICT) [2017R1A4A1015745]
- National Natural Science Foundation of China [U1705282, 22078066]
- BK21 Plus Program
- National Research Foundation of Korea [2017R1A4A1015745] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
The study demonstrates a clinically promising approach that combines a water-soluble phthalocyanine derivative and a hypoxia-activated prodrug to enhance the efficacy of PDT and improve cancer immunotherapy. This dual delivery method overcomes limitations of hypoxia in PDT and significantly activates CD8(+) T cells, showing potential for enhanced therapeutic outcomes in cancer treatment.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available