Overcoming Ovarian Cancer Drug Resistance with a Cold Responsive Nanomaterial
Authors: John P Fisher
Gang Zhao
Guang Ji
Christopher M Jewell
Pranay Agarwal
Xiongbin Lu
Hai Wang
Xiaoming He
Journal: ACS Central Science (2018)
Discipline: CHEMISTRY
Keywords: Drug resistance; membrane transporters; cancer stem cells; nanoparticles; hybrid nanoparticle
Affiliations: Fischell Department of Bioengineering and Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, Maryland 20742, United States., Department of Biomedical Engineering and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States., Center for Biomedical Engineering, Department of Electronic Science and Technology, University of Science and Technology of China, Hefei, Anhui 230027, China., Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China., Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland 21201, United States., Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States., United States Department of Veterans Affairs, Maryland VA Health Care System, Baltimore, Maryland 21201, United States., Department of Medical and Molecular Genetics and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.

Abstract:  Drug resistance due to overexpression of membrane transporters in cancer cells and the existence of cancer stem cells (CSCs) is a major hurdle to effective and safe cancer chemotherapy. Nanoparticles have been explored to overcome cancer drug resistance. However, drug slowly released from nanoparticles can still be efficiently pumped out of drug-resistant cells. Here, a hybrid nanoparticle of phospholipid and polymers is developed to achieve cold-triggered burst release of encapsulated drug. With ice cooling to below ∼12 °C for both burst drug release and reduced membrane transporter activity, binding of the drug with its target in drug-resistant cells is evident, while it is minimal in the cells kept at 37 °C. Moreover, targeted drug delivery with the cold-responsive nanoparticles in combination with ice cooling not only can effectively kill drug-resistant ovarian cancer cells and their CSCs in vitro but also destroy both subcutaneous and orthotopic ovarian tumors in vivo with no evident systemic toxicity. 

Retracted: No

PubPeer comments:
 Two images in Figure 7g appear to overlap. Seems to be a recurring issue with [one author] . *** ![file] , 
 Figure 6e appears to have two images which overlap with different coloration and orientation. If I am understanding correctly, these are differently treated mice, not serial sections stained differently. Apologies if I have misunderstood, but if I am correct it doesnu2019t seem possible for this to occur by accident. Very concerning. **Funding** This work was partially supported by American Cancer Society (# 120936-RSG-11-109-01-CDD) and NIH (R01CA206366). *** Original ![file] ![file] *** Black and white, contrast equalized ![file] *** ![file] , 
 Thank you very much for the comments! I ll talk to my co-authors and carefully address them ASAP. Best regards! , 
 https: forbetterscience.com 2021 04 19 xiongbin-lu-nanobombs-cancer-with-fluorescent-nude-mouse-recycling Indiana University Research Integrity Officer Shelley Bizila u201cMy office, IUu2019s Research Integrity Office, is responsible for receiving any allegations of possible falsification, fabrication or plagiarism and for administering IUu2019s policy. As such, our office has previously been made aware of the concerns you cite and has already started an inquiry process. We will proceed according to our policy to ensure any concerns of possible research misconduct are addressed. u201c , 
 May 17, 2021  We would like to make corrections to Figures 6e and 7g and the related Figures S30 (to Figure 6e) and S35 (to Figure 7g) (part of Supporting Information). In the figures, incorrect images were used by accident for the control conditions of either DOX (Figures 6e and S30) for tumor or DOX+I for spleen and lung (Figures 7g and S35), which occurred during the preparation of the figures. The original version (before correction) and corrected version of the images in these figures are provided. The corrections do not affect any conclusions or text (including the figure captions) of the original paper. Via https: pubs.acs.org doi pdf 10.1021 acscentsci.1c00530 , 
 I did not previously identify a possible issue in Supplemental Figure 33, where it appears that another set of images overlap. This does not seem to have been addressed in the correction. Could the authors please carefully review **all** the original files to help reassure readers that the original data supports the material presented in the paper? My skill set (such as it is) is limited to reviewing images, however this reader is concerned about the organizational challenges these problems suggest. *** ![file] , 
 Figure S15 excerpt. *** ![file] , 
 Figure S16. *** ![file] ,