Therapeutic dosing and targeting efficacy of Pt-Mal-LHRH towards triple negative breast cancer.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
31
12
2022
accepted:
31
05
2023
medline:
1
11
2023
pubmed:
10
10
2023
entrez:
10
10
2023
Statut:
epublish
Résumé
Pt-Mal-LHRH is a newly synthesized chemotherapeutic agent that was designed to selectively target the luteinizing hormone-releasing hormone (LHRH) receptor expressed by triple negative breast cancer (TNBC). The aim of this study was to evaluate the therapeutic dosing, tumor reduction efficacy, and selective distribution of Pt-Mal-LHRH in-vivo. LHRH tissue expression levels in-vivo were investigated using western blotting and LHRH was found to be increased in reproductive tissues (mammary, ovary, uterus). Further, Pt-Mal-LHRH was found to have increased TNBC tumor tissue platinum accumulation compared to carboplatin by inductively coupled plasma mass spectrometry analysis. The platinum family, compound carboplatin, was selected for comparison due to its similar chemical structure and molar equivalent doses were evaluated. Moreover, in-vivo distribution data indicated selective targeting of Pt-Mal-LHRH by enhanced reproductive tissue accumulation compared to carboplatin. Further, TNBC tumor growth was found to be significantly attenuated by Pt-Mal-LHRH compared to carboplatin in both the 4T1 and MDA-MB-231 tumor models. There was a significant reduction in tumor volume in the 4T1 tumor across Pt-Mal-LHRH doses (2.5-20 mg/kg/wk) and in the MDA-MB-231 tumor at the dose of 10 mg/kg/wk in models conducted by an independent contract testing laboratory. Our data indicates Pt-Mal-LHRH is a targeting chemotherapeutic agent towards the LHRH receptor and reduces TNBC tumor growth in-vivo. This study supports drug conjugation design models using the LHRH hormone for chemotherapeutic delivery as Pt-Mal-LHRH was found to be a more selective and efficacious than carboplatin. Further examination of Pt-Mal-LHRH is warranted for its clinical use in TNBCs, along with, other reproductive cancers overexpressing the LHRH receptor.
Identifiants
pubmed: 37816015
doi: 10.1371/journal.pone.0287151
pii: PONE-D-22-35750
pmc: PMC10564129
doi:
Substances chimiques
Receptors, LHRH
0
Carboplatin
BG3F62OND5
Platinum
49DFR088MY
Gonadotropin-Releasing Hormone
33515-09-2
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0287151Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103436
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL152392
Pays : United States
Informations de copyright
Copyright: © 2023 Ndinguri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
the authors have declared that no competing interests exist.
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