TY - JOUR
T1 - Water-Soluble Nanoconjugate for Enhanced Cellular Delivery of Receptor-Targeted Magnetic Resonance Contrast Agents
AU - Moore, Laura K.
AU - Caldwell, Michael A.
AU - Townsend, Taryn R.
AU - Macrenaris, Keith W.
AU - Moyle-Heyrman, Georgette
AU - Rammohan, Nikhil
AU - Schonher, Erika K.
AU - Burdette, Joanna E.
AU - Ho, Dean
AU - Meade, Thomas J.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/11/20
Y1 - 2019/11/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074280099&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.9b00640
DO - 10.1021/acs.bioconjchem.9b00640
M3 - Article
C2 - 31589412
AN - SCOPUS:85074280099
SN - 1043-1802
VL - 30
SP - 2947
EP - 2957
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 11
ER -