Engineered algae: A novel oxygen-generating system for effective treatment of hypoxic cancer
Authors: Zhen Du
Tingting Xie
Fei Yang
Zhimin Lu
Yangyang Li
Wanlin Li
Jianghong Rao
Danni Zhong
Yi Sun
Yuchen Qi
Min Zhou
Yue Qiao
Journal: Science Advances (2020)
Discipline: Multidisciplinary
Keywords: Microalgae; photosynthesis; biofuels; hypoxic tumor regions; oxygen levels
Affiliations: Eye Center & Key Laboratory of Cancer Prevention and Intervention, MOE, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China., Institute of Translational Medicine and The Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China., Department of Radiology and Bio-X, Stanford University, Stanford, CA 94305, USA., Division of Radiation and Cancer Biology, Department of Radiation Oncology 94305, University of Michigan, Ann Arbor, MI 48109, USA., State Key Laboratory of Modern Optical Instrumentations, Zhejiang University, Hangzhou 310058, China.

Abstract:  Microalgae, a naturally present unicellular microorganism, can undergo light photosynthesis and have been used in biofuels, nutrition, etc. Here, we report that engineered live microalgae can be delivered to hypoxic tumor regions to increase local oxygen levels and resensitize resistant cancer cells to both radio- and phototherapies. We demonstrate that the hypoxic environment in tumors is markedly improved by in situ-generated oxygen through microalgae-mediated photosynthesis, resulting in notably radiotherapeutic efficacy. Furthermore, the chlorophyll from microalgae produces reactive oxygen species during laser irradiation, further augmenting the photosensitizing effect and enhancing tumor cell apoptosis. Thus, the sequential combination of oxygen-generating algae system with radio- and phototherapies has the potential to create an innovative treatment strategy to improve the outcome of cancer management. Together, our findings demonstrate a novel approach that leverages the products of photosynthesis for treatment of tumors and provide proof-of-concept evidence for future development of algae-enhanced radio- and photodynamic therapy. 

Retracted: No

PubPeer comments:
 Figure 2A. * Green boxes: The Hypoxia 5% O2 1h panel appears to show an overlap with the Hypoxia 1% O2 2h panel. Of note, the red signal is much lower in the latter panel, suggesting this is not a simple misplaced image. * Pink boxes: The Hypoxia 1% O2 1h appears to show an overlap with the Hypoxia 5% O2 5h panel. Here as well, the panels differ in the red signal. ![file] , 
 Brought to my attention by a reader. Figure 3A. * Red boxes: The mouse photos at 0h and 48h appear to look very similar. After lying there for 48h, and clearly moving around a bit as shown by the other photos, did the mouse happen to move back to the exact same position, or could the authors please check if there was a mix up of the photos? ![file] , 
 Brought to my attention by the same reader as comment #2. Figure 4F and 5D. * Yellow boxes: In the H E staining, the RBCM-Algae tumor tissue looks the same as the 2h RBCM-Algae+RT+Laser tumor. Could the authors please check? ![file] , 
 Thanks for bringing this to our attention. I have forwarded the comments to the coauthors who did the experiments, and they are checking the original data. Will get back to you. , 
 #3 Thanks for pointing out the errors in the figures. I have contacted the first authors who performed the experiments, and will double check the original data. We will send you our response ASAP. , 
 #1 Dear Dr. Elisabeth M Bik, Thank you for reminding us of the errors. We accidentally misplaced three panels of photos in Figures 2A and 4F After carefully examining our original data, we found that the errors were caused by our carelessness in exporting the representative confocal images and compiling these figures. We have now replaced these misplaced panels with correct ones. We have also shown the entire mouse photos in Figure 3A, which demonstrated a slightly different position at 0 vs. 48 hrs. We assure that the data presented now are real and reliable without any subjective processing. We apologize for such unconscious error, which may cause the confusion to the readers. We would also like to state that the image substitutions do not affect any results presented in the originally-published version, nor the corresponding text description and the conclusion of the paper. Here are the corrected figures, which will be sent shortly to the journal publisher for the error correction. Thank you again for helping us to find and correct these errors. Sincerely, Yue Qiao, Fei Yang (the first authors of the paper) ![file] ![file] ![file] ,