UMMS Affiliation

RNA Therapeutics Institute; Department of Psychiatry, Center for Comparative NeuroImaging

Publication Date

2020-05-19

Document Type

Article

Disciplines

Medicinal and Pharmaceutical Chemistry | Neoplasms | Therapeutics

Abstract

Bulk chemotherapy and drug release strategies for cancer treatment have been associated with lack of specificity and high drug concentrations that often result in toxic side effects. This work presents the results of an experimental study of cancer drugs (prodigiosin or paclitaxel) conjugated to Luteinizing Hormone-Releasing Hormone (LHRH) for the specific targeting and treatment of triple negative breast cancer (TNBC). Injections of LHRH-conjugated drugs (LHRH-prodigiosin or LHRH-paclitaxel) into groups of 4-week-old athymic female nude mice (induced with subcutaneous triple negative xenograft breast tumors) were found to specifically target, eliminate or shrink tumors at early, mid and late stages without any apparent cytotoxicity, as revealed by in vivo toxicity and ex vivo histopathological tests. Our results show that overexpressed LHRH receptors serve as binding sites on the breast cancer cells/tumor and the LHRH-conjugated drugs inhibited the growth of breast cells/tumor in in vitro and in vivo experiments. The inhibitions are attributed to the respective adhesive interactions between LHRH molecular recognition units on the prodigiosin (PGS) and paclitaxel (PTX) drugs and overexpressed LHRH receptors on the breast cancer cells and tumors. The implications of the results are discussed for the development of ligand-conjugated drugs for the specific targeting and treatment of TNBC.

Keywords

Breast cancer, Drug delivery

Rights and Permissions

© The Author(s) 2020. 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 http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1038/s41598-020-64979-1

Source

Obayemi JD, Salifu AA, Eluu SC, Uzonwanne VO, Jusu SM, Nwazojie CC, Onyekanne CE, Ojelabi O, Payne L, Moore CM, King JA, Soboyejo WO. LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer. Sci Rep. 2020 May 19;10(1):8212. doi: 10.1038/s41598-020-64979-1. PMID: 32427904; PMCID: PMC7237454. Link to article on publisher's site

Journal/Book/Conference Title

Scientific reports

Related Resources

Link to Article in PubMed

PubMed ID

32427904

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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