Research Paper Volume 13, Issue 1 pp 1383—1409
The therapeutic significance of the novel photodynamic material TPE-IQ-2O in tumors
- 1 Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- 2 Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- 3 Department of Pathology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Received: June 24, 2020 Accepted: October 21, 2020 Published: December 19, 2020
https://doi.org/10.18632/aging.202355How to Cite
Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Combination therapies based on photodynamic therapy (PDT) have received much attention in various cancers due to their strong therapeutic effects. Here, we aimed to explore the safety and effectiveness of a new mitochondria-targeting photodynamic material, TPE-IQ-2O, in combination therapies (combined with surgery or immunotherapy). The safety and effectiveness of TPE-IQ-2O PDT were verified with cytotoxicity evaluation in vitro and a zebrafish xenograft model in vivo, respectively. The effectiveness of TPE-IQ-2O PDT combined with surgery or immune checkpoint inhibitors (ICIs) was verified in tumor-bearing mice. Small animal in vivo imaging, immunohistochemistry, and flow cytometry were used to determine the underlying mechanism. TPE-IQ-2O PDT can not only reduce tumor recurrence in surgical treatment but also effectively improve the response to ICIs in immunotherapy without obvious toxicity. It was also found to ameliorate the immunosuppressive tumor microenvironment and promote the antitumor immunity induced by ICIs by increasing CD8+ tumor-infiltrating lymphocyte accumulation. Thus, TPE-IQ-2O PDT is a safe and effective antitumor therapy that can be combined with surgery or immunotherapy.
Abbreviations
5-ALA: 5-Aminolevulinic acid; ACQ: aggregation-caused quenching; AIE: aggregation-induced emissi; BEGM: Bronchial Epithelial Growth Medium; CAS: Chinese Academy of Sciences; CCK-8: Cell Counting Kit-8; CCTC: China Center for Type Culture Collection; DEV: the model in which KYSE-30 cells were directly injected into the mouse esophageal mucosa; DMEM: Dulbecco’s modified Eagle’s medium; DMSO: dimethyl sulfoxide; EV/SN: the model in which KYSE-30 cells were injected into the esophageal mucosa after subcutaneous tumor formation; FBS: fetal bovine serum; FFPE: formalin-fixed, paraffin-embedded; FITC: fluorescein isothiocyanate; Fs: femtosecond; HE: Hematoxylin and eosin; HUVECs: human umbilical vein endothelial cells; ICIs: immune checkpoint inhibitors; IHC: Immunohistochemistry; LLC: Lewis lung carcinoma; MTDR: MitoTracker Deep Red; PBS: Phosphate-buffered saline; PD-1: programmed death 1; PD-L1: Programmed cell death ligand 1; PS: photosensitizer; ROI: rectangular region of interest; ROS: reactive oxygen species; SHG: Second-harmonic generation; SPF: specific-pathogen free; TILs: Tumor-infiltrating lymphocytes.