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A self-internalizing mitochondrial TSPO targeting imaging probe for fluorescence, MRI and EM.

ABSTRACT: Advances in probes for cellular imaging have driven discoveries in biology and medicine. Primarily, antibodies and small molecules have been made for contrast enhancement of specific proteins. The development of new dendrimer-based tools offers opportunities to tune cellular internalization and targeting, image multiple modalities in the same molecule and explore therapeutics. The translocator protein (TSPO) offers an ideal target to develop dendrimer tools because it is well characterized and implicated in a number of disease states. The TSPO-targeted dendrimers reported here, primarily ClPhIQ-PAMAM-Gd-Liss, are cell membrane permeable nanoparticles that enable labeling of TSPO and provide contrast in fluorescence, electron microscopy and magnetic resonance imaging. The molecular binding affinity for TSPO was found to be 0.51 ?M, 3 times greater than the monomeric agents previously demonstrated in our laboratory. The relaxivity per Gd3+ of the ClPhIQ23-PAMAM-Gd18 dendrimer was 7.7 and 8.0 mM-1 s-1 for r 1 and r 2 respectively, approximately double that of the clinically used monomeric Gd3+ chelates. In vitro studies confirmed molecular selectively for labeling TSPO in the mitochondria of C6 rat glioma and MDA-MB-231 cell lines. Fluorescence co-registration with Mitotracker Green® and increased contrast of osmium-staining in electron microscopy confirmed mitochondrial labeling of these TSPO-targeted agents. Taken collectively these experiments demonstrate the versatility of conjugation of our PAMAM dendrimeric chemistry to allow multi-modality agents to be prepared. These agents target organelles and use complementary imaging modalities in vitro, potentially allowing disease mechanism studies with high sensitivity and high resolution techniques.

SUBMITTER: Samuelson LE

PROVIDER: S-EPMC7015156 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A self-internalizing mitochondrial TSPO targeting imaging probe for fluorescence, MRI and EM.

Samuelson Lynn E LE Anderson Bernard M BM Bai Mingfeng M Dukes Madeline J MJ Hunt Colette R CR Casey Jonathon D JD Han Zeqiu Z Papadopoulos Vassilios V Bornhop Darryl J DJ

RSC advances 20140103 18

Advances in probes for cellular imaging have driven discoveries in biology and medicine. Primarily, antibodies and small molecules have been made for contrast enhancement of specific proteins. The development of new dendrimer-based tools offers opportunities to tune cellular internalization and targeting, image multiple modalities in the same molecule and explore therapeutics. The translocator protein (TSPO) offers an ideal target to develop dendrimer tools because it is well characterized and i ...[more]

PMID: 32051760

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Dataset Information

A self-internalizing mitochondrial TSPO targeting imaging probe for fluorescence, MRI and EM.

Publications

A self-internalizing mitochondrial TSPO targeting imaging probe for fluorescence, MRI and EM.

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