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Protein-coated corrole nanoparticles for the treatment of prostate cancer cells

Soll, Matan and Chen, Qiu-Cheng and Zhitomirsky, Benny and Lim, Punnajit P. and Termini, John and Gray, Harry B. and Assaraf, Yehuda G. and Gross, Zeev (2020) Protein-coated corrole nanoparticles for the treatment of prostate cancer cells. Cell Death Discovery, 6 . Art. No. 67. ISSN 2058-7716. PMCID PMC7387447.

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Development of novel therapeutic strategies to eradicate malignant tumors is of paramount importance in cancer research. In a recent study, we have introduced a facile protocol for the preparation of corrole-protein nanoparticles (NPs). These NPs consist of a corrole-core coated with protein. We now report that a novel lipophilic corrole, (2)Ga, delivered as human serum albumin (HSA)-coated NPs, displayed antineoplastic activity towards human prostate cancer DU-145 cells. Cryo-TEM analysis of these NPs revealed an average diameter of 50.2 ± 8.1 nm with a spherical architecture exhibiting low polydispersity. In vitro cellular uptake of (2)Ga/albumin NPs was attributable to rapid internalization of the corrole through ligand binding-dependent extracellular release and intercalation of the corrole cargo into the lipid bilayer of the plasma membrane. This finding is in contrast with a previously reported study on corrole-protein NPs that displayed cellular uptake via endocytosis. Investigation of the non-light-induced mechanism of action of (2)Ga suggested the induction of necrosis through plasma membrane destabilization, impairment of calcium homeostasis, lysosomal stress and rupture, as well as formation of reactive oxygen species (ROS). (2)Ga also exhibited potent light-induced cytotoxicity through ROS generation. These findings demonstrate a rapid cellular uptake of (2)Ga/protein NPs along with targeted induction of tumor cell necrosis.

Item Type:Article
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URLURL TypeDescription CentralArticle
Chen, Qiu-Cheng0000-0001-5113-4832
Lim, Punnajit P.0000-0002-0159-1549
Termini, John0000-0002-4043-7552
Gray, Harry B.0000-0002-7937-7876
Assaraf, Yehuda G.0000-0001-6692-8221
Gross, Zeev0000-0003-1170-2115
Additional Information:© 2020 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Received: 11 December 2019. Revised: 18 May 2020. Accepted: 28 May 2020. Published online: 28 July 2020. The work by HBG at the California Institute of Technology was supported by NIH R01DK019038. Research at the City of Hope (J.T.) and at Technion (Z.G.) was supported by an International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars Program, a partnership of the ICRF and City of Hope funded by the Harvey L. Miller Family Foundation. The authors declare no conflict of interests.
Funding AgencyGrant Number
Israel Cancer Research FundUNSPECIFIED
Harvey L. Miller Family FoundationUNSPECIFIED
PubMed Central ID:PMC7387447
Record Number:CaltechAUTHORS:20200813-094027297
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Official Citation:Soll, M., Chen, Q., Zhitomirsky, B. et al. Protein-coated corrole nanoparticles for the treatment of prostate cancer cells. Cell Death Discov. 6, 67 (2020).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104953
Deposited By: George Porter
Deposited On:13 Aug 2020 18:23
Last Modified:14 Aug 2020 15:58

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