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Article

Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent

1
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
2
Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Sudip K. Das
Pharmaceutics 2022, 14(3), 527; https://doi.org/10.3390/pharmaceutics14030527
Received: 20 January 2022 / Revised: 21 February 2022 / Accepted: 25 February 2022 / Published: 27 February 2022
(This article belongs to the Topic Targeting Tumor Metabolism for Cancer Therapy)
Nano-catalytic agents actuating Fenton-like reaction in cancer cells cause intratumoral generation of reactive oxygen species (ROS), allowing the potential for immune therapy of tumor metastasis via the recognition of tumor-associated antigens. However, the self-defense mechanism of cancer cells, known as autophagy, and unsustained ROS generation often restricts efficiency, lowering the immune attack, especially in invading metastatic clusters. Here, a functional core-shell metal-organic framework nanocube (dual MOF) doubling as a catalytic agent and T cell infiltration inducer that programs ROS and inhibits autophagy is reported. The dual MOF integrated a Prussian blue (PB)-coated iron (Fe2+)-containing metal-organic framework (MOF, MIL88) as a programmed peroxide mimic in the cancer cells, facilitating the sustained ROS generation. With the assistance of Chloroquine (CQ), the inhibition of autophagy through lysosomal deacidification breaks off the self-defense mechanism and further improves the cytotoxicity. The purpose of this material design was to inhibit autophagy and ROS efficacy of the tumor, and eventually improve T cell recruitment for immune therapy of lung metastasis. The margination and internalization-mediated cancer cell uptake improve the accumulation of dual MOF of metastatic tumors in vivo. The effective catalytic dual MOF integrated dysfunctional autophagy at the metastasis elicits the ~3-fold recruitment of T lymphocytes. Such synergy of T cell recruitment and ROS generation transported by dual MOF during the metastases successfully suppresses more than 90% of tumor foci in the lung. View Full-Text
Keywords: drug delivery; nano-catalytic medicine; MOF; autophagy; immune response; lung metastasis drug delivery; nano-catalytic medicine; MOF; autophagy; immune response; lung metastasis
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MDPI and ACS Style

Nirosha Yalamandala, B.; Chen, P.-H.; Moorthy, T.; Huynh, T.M.H.; Chiang, W.-H.; Hu, S.-H. Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent. Pharmaceutics 2022, 14, 527. https://doi.org/10.3390/pharmaceutics14030527

AMA Style

Nirosha Yalamandala B, Chen P-H, Moorthy T, Huynh TMH, Chiang W-H, Hu S-H. Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent. Pharmaceutics. 2022; 14(3):527. https://doi.org/10.3390/pharmaceutics14030527

Chicago/Turabian Style

Nirosha Yalamandala, Bhanu, Pin-Hua Chen, Thrinayan Moorthy, Thi M.H. Huynh, Wen-Hsuan Chiang, and Shang-Hsiu Hu. 2022. "Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent" Pharmaceutics 14, no. 3: 527. https://doi.org/10.3390/pharmaceutics14030527

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