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Cell-Penetrating Protein/Corrole Nanoparticles

Soll, Matan and Goswami, Tridib K. and Chen, Qiu-Cheng and Saltsman, Irena and Teo, Ruijie D. and Shahgholi, Mona and Lim, Punnajit and Di Bilio, Angel J. and Cohen, Sarah and Termini, John and Gray, Harry B. and Gross, Zeev (2019) Cell-Penetrating Protein/Corrole Nanoparticles. Scientific Reports, 9 . Art. No. 2294. ISSN 2045-2322. PMCID PMC6381154. https://resolver.caltech.edu/CaltechAUTHORS:20190219-134141446

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Abstract

Recent work has highlighted the potential of metallocorroles as versatile platforms for the development of drugs and imaging agents, since the bioavailability, physicochemical properties and therapeutic activity can be dramatically altered by metal ion substitution and/or functional group replacement. Significant advances in cancer treatment and imaging have been reported based on work with a water-soluble bis-sulfonated gallium corrole in both cellular and rodent-based models. We now show that cytotoxicities increase in the order Ga < Fe < Al < Mn < Sb < Au for bis-sulfonated corroles; and, importantly, that they correlate with metallocorrole affinities for very low density lipoprotein (VLDL), the main carrier of lipophilic drugs. As chemotherapeutic potential is predicted to be enhanced by increased lipophilicity, we have developed a novel method for the preparation of cell-penetrating lipophilic metallocorrole/serum-protein nanoparticles (NPs). Cryo-TEM revealed an average core metallocorrole particle size of 32 nm, with protein tendrils extending from the core (conjugate size is ~100 nm). Optical imaging of DU-145 prostate cancer cells treated with corrole NPs (≤100 nM) revealed fast cellular uptake, very slow release, and distribution into the endoplasmic reticulum (ER) and lysosomes. The physical properties of corrole NPs prepared in combination with transferrin and albumin were alike, but the former were internalized to a greater extent by the transferrin-receptor-rich DU-145 cells. Our method of preparation of corrole/protein NPs may be generalizable to many bioactive hydrophobic molecules to enhance their bioavailability and target affinity.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41598-019-38592-wDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381154PubMed CentralArticle
ORCID:
AuthorORCID
Chen, Qiu-Cheng0000-0001-5113-4832
Teo, Ruijie D.0000-0003-2203-9662
Lim, Punnajit0000-0002-0159-1549
Termini, John0000-0002-4043-7552
Gray, Harry B.0000-0002-7937-7876
Additional Information:© 2019 The Author(s). 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 http://creativecommons.org/licenses/by/4.0/. Received 19 June 2018; Accepted 18 December 2018; Published 19 February 2019. This study 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, as supported by The Harvey L. Miller Family Foundation to ZG and JT. Research at Caltech was supported by the National Institutes of Health (DK-019038 to HBG). Initial support from the Caltech/City of Hope Biomedical Initiative to HBG and JT also is gratefully acknowledged. Author Contributions: Most of the experimental work was done by M.S. at the Technion, with contributions by T.K.G. for the human serum binding studies, Q.C.C. and S.C. for the TF HPLC analyses, P.L., R.D.T. and A.J.D.B. for the cytotoxicity studies, and I.S. for the catalysis reactions. M.S.h. performed the MALDI-MS. M.S., J.T., H.B.G. and Z.G. wrote the article. The project was supervised by J.T., H.B.G. and Z.G. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Jacki and Bruce Barron Cancer Research Scholars’ ProgramUNSPECIFIED
Harvey L. Miller Family FoundationUNSPECIFIED
NIHDK-019038
Caltech-City of Hope Biomedical InitiativeUNSPECIFIED
Subject Keywords:Cancer imaging; Nanoparticles
PubMed Central ID:PMC6381154
Record Number:CaltechAUTHORS:20190219-134141446
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190219-134141446
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92984
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Feb 2019 21:54
Last Modified:09 Mar 2020 13:19

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