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Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy
[Image: see text] In nanomedicine, determining the spatial distribution of particles and drugs, together and apart, at high resolution within tissues, remains a major challenge because each must have a different label or detectable feature that can be observed with high sensitivity and resolution. W...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276039/ https://www.ncbi.nlm.nih.gov/pubmed/30555899 http://dx.doi.org/10.1021/acscentsci.8b00444 |
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author | Proetto, Maria T. Callmann, Cassandra E. Cliff, John Szymanski, Craig J. Hu, Dehong Howell, Stephen B. Evans, James E. Orr, Galya Gianneschi, Nathan C. |
author_facet | Proetto, Maria T. Callmann, Cassandra E. Cliff, John Szymanski, Craig J. Hu, Dehong Howell, Stephen B. Evans, James E. Orr, Galya Gianneschi, Nathan C. |
author_sort | Proetto, Maria T. |
collection | PubMed |
description | [Image: see text] In nanomedicine, determining the spatial distribution of particles and drugs, together and apart, at high resolution within tissues, remains a major challenge because each must have a different label or detectable feature that can be observed with high sensitivity and resolution. We prepared nanoparticles capable of enzyme-directed assembly of particle therapeutics (EDAPT), containing an analogue of the Pt(II)-containing drug oxaliplatin, an (15)N-labeled monomer in the hydrophobic block of the backbone of the polymer, the near-infrared dye Cy5.5, and a peptide that is a substrate for tumor metalloproteinases in the hydrophilic block. When these particles reach an environment rich in tumor associated proteases, the hydrophilic peptide substrate is cleaved, causing the particles to accumulate through a morphology transition, locking them in the tumor extracellular matrix. To evaluate the distribution of drug and EDAPT carrier in vivo, the localization of the isotopically labeled polymer backbone was compared to that of Pt by nanoscale secondary ion mass spectrometry (NanoSIMS). The correlation of NanoSIMS with super-resolution fluorescence microscopy revealed the release of the drug from the nanocarrier and colocalization with cellular DNA within tumor tissue. The results confirmed the dependence of particle accumulation and Pt(II) drug delivery on the presence of a Matrix Metalloproteinase (MMP) substrate and demonstrated antitumor activity. We conclude that these techniques are powerful for the elucidation of the localization of cargo and carrier, and enable a high-resolution assessment of their performance following in vivo delivery. |
format | Online Article Text |
id | pubmed-6276039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-62760392018-12-15 Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy Proetto, Maria T. Callmann, Cassandra E. Cliff, John Szymanski, Craig J. Hu, Dehong Howell, Stephen B. Evans, James E. Orr, Galya Gianneschi, Nathan C. ACS Cent Sci [Image: see text] In nanomedicine, determining the spatial distribution of particles and drugs, together and apart, at high resolution within tissues, remains a major challenge because each must have a different label or detectable feature that can be observed with high sensitivity and resolution. We prepared nanoparticles capable of enzyme-directed assembly of particle therapeutics (EDAPT), containing an analogue of the Pt(II)-containing drug oxaliplatin, an (15)N-labeled monomer in the hydrophobic block of the backbone of the polymer, the near-infrared dye Cy5.5, and a peptide that is a substrate for tumor metalloproteinases in the hydrophilic block. When these particles reach an environment rich in tumor associated proteases, the hydrophilic peptide substrate is cleaved, causing the particles to accumulate through a morphology transition, locking them in the tumor extracellular matrix. To evaluate the distribution of drug and EDAPT carrier in vivo, the localization of the isotopically labeled polymer backbone was compared to that of Pt by nanoscale secondary ion mass spectrometry (NanoSIMS). The correlation of NanoSIMS with super-resolution fluorescence microscopy revealed the release of the drug from the nanocarrier and colocalization with cellular DNA within tumor tissue. The results confirmed the dependence of particle accumulation and Pt(II) drug delivery on the presence of a Matrix Metalloproteinase (MMP) substrate and demonstrated antitumor activity. We conclude that these techniques are powerful for the elucidation of the localization of cargo and carrier, and enable a high-resolution assessment of their performance following in vivo delivery. American Chemical Society 2018-10-23 2018-11-28 /pmc/articles/PMC6276039/ /pubmed/30555899 http://dx.doi.org/10.1021/acscentsci.8b00444 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Proetto, Maria T. Callmann, Cassandra E. Cliff, John Szymanski, Craig J. Hu, Dehong Howell, Stephen B. Evans, James E. Orr, Galya Gianneschi, Nathan C. Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy |
title | Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded
Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry
and Fluorescence Microscopy |
title_full | Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded
Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry
and Fluorescence Microscopy |
title_fullStr | Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded
Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry
and Fluorescence Microscopy |
title_full_unstemmed | Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded
Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry
and Fluorescence Microscopy |
title_short | Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded
Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry
and Fluorescence Microscopy |
title_sort | tumor retention of enzyme-responsive pt(ii) drug-loaded
nanoparticles imaged by nanoscale secondary ion mass spectrometry
and fluorescence microscopy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276039/ https://www.ncbi.nlm.nih.gov/pubmed/30555899 http://dx.doi.org/10.1021/acscentsci.8b00444 |
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