| Literature DB >> 31589412 |
Laura K Moore1, Michael A Caldwell2, Taryn R Townsend2, Keith W MacRenaris2, Georgette Moyle-Heyrman3, Nikhil Rammohan2, Erika K Schonher2, Joanna E Burdette3, Dean Ho4,5, Thomas J Meade1,2.
Abstract
ProGlo is an efficient steroid receptor-targeted magnetic resonance (MR) imaging contrast agent (CA). It has been shown to bind to the progesterone receptor (PR) and produce enhanced image contrast in PR-positive cells and tissues in vitro and in vivo. However, the hydrophobicity of the steroid targeting domain of ProGlo (logP = 1.4) limits its formulation and delivery at clinically relevant doses. In this work, a hydrophobic moiety was utilized to drive efficient adsorption onto nanodiamond (ND) clusters to form a water-soluble nanoconstruct (logP = -2.4) with 80% release in 8 h under biological conditions. In cell culture, the ND-ProGlo construct delivered increased concentrations of ProGlo to target cells compared to ProGlo alone. Importantly, these results were accomplished without the use of solvents such as DMSO, providing a significant advance toward formulating ProGlo for translational applications. Biodistribution studies confirm the delivery of ProGlo to PR(+) tissues with enhanced efficacy over untargeted controls. These results demonstrate the potential for a noncovalent ND-CA construct as a general strategy for solubilizing and delivering hydrophobic targeted MR CAs.Entities:
Year: 2019 PMID： 31589412 PMCID： PMC6868311 DOI： 10.1021/acs.bioconjchem.9b00640
Source DB: PubMed Journal: Bioconjug Chem ISSN： 1043-1802 Impact factor: 4.774