Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers

Kezheng Wang; Dipanjan Pan; Anne H. Schmieder; Angana Senpan; Dennis E. Hourcade; Christine T.N. Pham; Lynne M. Mitchell; Shelton D. Caruthers; Grace Cui; Samuel A. Wickline; Baozhong Shen; Gregory M. Lanza

doi:10.1016/j.nano.2014.12.009

Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers

Kezheng Wang, Dipanjan Pan, Anne H. Schmieder, Angana Senpan, Dennis E. Hourcade, Christine T.N. Pham, Lynne M. Mitchell, Shelton D. Caruthers, Grace Cui, Samuel A. Wickline, Baozhong Shen, Gregory M. Lanza

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10 Scopus citations

Abstract

High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (D_av)/nm; PDI: 0.06; zeta: -27 ± 2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk.

Original language	English
Pages (from-to)	601-609
Number of pages	9
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	11
Issue number	3
DOIs	https://doi.org/10.1016/j.nano.2014.12.009
State	Published - 2015

Keywords

Complement activation
Contrast media
Gadolinium
MRI
Manganese
Nanoparticle

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10.1016/j.nano.2014.12.009

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Wang, K., Pan, D., Schmieder, A. H., Senpan, A., Hourcade, D. E., Pham, C. T. N., Mitchell, L. M., Caruthers, S. D., Cui, G., Wickline, S. A., Shen, B., & Lanza, G. M. (2015). Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers. Nanomedicine: Nanotechnology, Biology, and Medicine, 11(3), 601-609. https://doi.org/10.1016/j.nano.2014.12.009

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title = "Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers",

abstract = "High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (Dav)/nm; PDI: 0.06; zeta: -27 ± 2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk.",

keywords = "Complement activation, Contrast media, Gadolinium, MRI, Manganese, Nanoparticle",

author = "Kezheng Wang and Dipanjan Pan and Schmieder, {Anne H.} and Angana Senpan and Hourcade, {Dennis E.} and Pham, {Christine T.N.} and Mitchell, {Lynne M.} and Caruthers, {Shelton D.} and Grace Cui and Wickline, {Samuel A.} and Baozhong Shen and Lanza, {Gregory M.}",

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year = "2015",

doi = "10.1016/j.nano.2014.12.009",

language = "English",

volume = "11",

pages = "601--609",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

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Wang, K, Pan, D, Schmieder, AH, Senpan, A, Hourcade, DE, Pham, CTN, Mitchell, LM, Caruthers, SD, Cui, G, Wickline, SA, Shen, B & Lanza, GM 2015, 'Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 11, no. 3, pp. 601-609. https://doi.org/10.1016/j.nano.2014.12.009

TY - JOUR

T1 - Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers

AU - Wang, Kezheng

AU - Pan, Dipanjan

AU - Schmieder, Anne H.

AU - Senpan, Angana

AU - Hourcade, Dennis E.

AU - Pham, Christine T.N.

AU - Mitchell, Lynne M.

AU - Caruthers, Shelton D.

AU - Cui, Grace

AU - Wickline, Samuel A.

AU - Shen, Baozhong

AU - Lanza, Gregory M.

PY - 2015

Y1 - 2015

N2 - High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (Dav)/nm; PDI: 0.06; zeta: -27 ± 2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk.

AB - High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (Dav)/nm; PDI: 0.06; zeta: -27 ± 2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk.

KW - Complement activation

KW - Contrast media

KW - Gadolinium

KW - MRI

KW - Manganese

KW - Nanoparticle

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AN - SCOPUS:84933527413

SN - 1549-9634

VL - 11

SP - 601

EP - 609

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

IS - 3

ER -

Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers

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