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

Title
In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer
Authors
Li X.Jeon Y.-H.Kwon N.Park J.-G.Guo T.Kim H.-R.Huang J.-D.Lee D.-S.Yoon J.
Ewha Authors
윤주영
SCOPUS Author ID
윤주영scopus
Issue Date
2021
Journal Title
Biomaterials
ISSN
0142-9612JCR Link
Citation
Biomaterials vol. 266
Keywords
Cancer immunotherapyHypoxia-activated prodrugPhotodynamic therapyPhthalocyanineSupramolecular self-assembly
Publisher
Elsevier Ltd
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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. © 2020 Elsevier Ltd
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DOI
10.1016/j.biomaterials.2020.120430
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자연과학대학 > 화학·나노과학전공 > Journal papers
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