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High-resolution 3D visualization of nanomedicine distribution in tumors

To improve the clinical translation of anti-cancer nanomedicines, it is necessary to begin building specific insights into the broad concept of the Enhanced Permeability and Retention (EPR) effect, using detailed investigations of the accumulation, distribution and retention of nanomedicines in soli...

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Autores principales: Moss, Jennifer I., Barjat, Hervé, Emmas, Sally-Ann, Strittmatter, Nicole, Maynard, Juliana, Goodwin, Richard J. A., Storm, Gert, Lammers, Twan, Puri, Sanyogitta, Ashford, Marianne B., Barry, Simon T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929971/
https://www.ncbi.nlm.nih.gov/pubmed/31903157
http://dx.doi.org/10.7150/thno.37178
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author Moss, Jennifer I.
Barjat, Hervé
Emmas, Sally-Ann
Strittmatter, Nicole
Maynard, Juliana
Goodwin, Richard J. A.
Storm, Gert
Lammers, Twan
Puri, Sanyogitta
Ashford, Marianne B.
Barry, Simon T.
author_facet Moss, Jennifer I.
Barjat, Hervé
Emmas, Sally-Ann
Strittmatter, Nicole
Maynard, Juliana
Goodwin, Richard J. A.
Storm, Gert
Lammers, Twan
Puri, Sanyogitta
Ashford, Marianne B.
Barry, Simon T.
author_sort Moss, Jennifer I.
collection PubMed
description To improve the clinical translation of anti-cancer nanomedicines, it is necessary to begin building specific insights into the broad concept of the Enhanced Permeability and Retention (EPR) effect, using detailed investigations of the accumulation, distribution and retention of nanomedicines in solid tumors. Nanomedicine accumulation in preclinical tumors has been extensively studied; however, treatment efficacy will be heavily influenced by both the quantity of drug-loaded nanomedicines reaching the tumor as well as their spatial distribution throughout the tumor. It remains a challenge to image the heterogeneity of nanomedicine distribution in 3 dimensions within solid tumors with a high degree of spatial resolution using standard imaging approaches. Methods: To achieve this, an ex vivo micro computed tomography (µCT) imaging approach was developed to visualize the intratumoral distribution of contrast agent-loaded PEGylated liposomes. Using this semi-quantitative method, whole 3-dimensional (3D) tumor liposome distribution was determined with 17 µm resolution in a phenotypically diverse panel of four preclinical xenograft and patient-derived explant (PDX) tumor models. Results: High-resolution ex vivo μCT imaging revealed striking differences in liposome distribution within tumors in four models with different vascular patterns and densities, stromal contents, and microenvironment morphologies. Following intravenous dosing, the model with the highest density of pericyte-supported vessels showed the greatest liposome accumulation, while the model with vessels present in regions of high α-smooth muscle actin (αSMA) content presented with a large proportion of the liposomes at depths beyond the tumor periphery. The two models with an unsupported vascular network demonstrated a more restricted pattern of liposome distribution. Conclusion: Taken together, vessel distribution and support (the latter indicative of functionality) appear to be key factors determining the accumulation and distribution pattern of liposomes in tumors. Our findings demonstrate that high-resolution 3D visualization of nanomedicine distribution is a useful tool for preclinical nanomedicine research, providing valuable insights into the influence of the tumor vasculature and microenvironment on nanomedicine localization.
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spelling pubmed-69299712020-01-04 High-resolution 3D visualization of nanomedicine distribution in tumors Moss, Jennifer I. Barjat, Hervé Emmas, Sally-Ann Strittmatter, Nicole Maynard, Juliana Goodwin, Richard J. A. Storm, Gert Lammers, Twan Puri, Sanyogitta Ashford, Marianne B. Barry, Simon T. Theranostics Research Paper To improve the clinical translation of anti-cancer nanomedicines, it is necessary to begin building specific insights into the broad concept of the Enhanced Permeability and Retention (EPR) effect, using detailed investigations of the accumulation, distribution and retention of nanomedicines in solid tumors. Nanomedicine accumulation in preclinical tumors has been extensively studied; however, treatment efficacy will be heavily influenced by both the quantity of drug-loaded nanomedicines reaching the tumor as well as their spatial distribution throughout the tumor. It remains a challenge to image the heterogeneity of nanomedicine distribution in 3 dimensions within solid tumors with a high degree of spatial resolution using standard imaging approaches. Methods: To achieve this, an ex vivo micro computed tomography (µCT) imaging approach was developed to visualize the intratumoral distribution of contrast agent-loaded PEGylated liposomes. Using this semi-quantitative method, whole 3-dimensional (3D) tumor liposome distribution was determined with 17 µm resolution in a phenotypically diverse panel of four preclinical xenograft and patient-derived explant (PDX) tumor models. Results: High-resolution ex vivo μCT imaging revealed striking differences in liposome distribution within tumors in four models with different vascular patterns and densities, stromal contents, and microenvironment morphologies. Following intravenous dosing, the model with the highest density of pericyte-supported vessels showed the greatest liposome accumulation, while the model with vessels present in regions of high α-smooth muscle actin (αSMA) content presented with a large proportion of the liposomes at depths beyond the tumor periphery. The two models with an unsupported vascular network demonstrated a more restricted pattern of liposome distribution. Conclusion: Taken together, vessel distribution and support (the latter indicative of functionality) appear to be key factors determining the accumulation and distribution pattern of liposomes in tumors. Our findings demonstrate that high-resolution 3D visualization of nanomedicine distribution is a useful tool for preclinical nanomedicine research, providing valuable insights into the influence of the tumor vasculature and microenvironment on nanomedicine localization. Ivyspring International Publisher 2020-01-01 /pmc/articles/PMC6929971/ /pubmed/31903157 http://dx.doi.org/10.7150/thno.37178 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Moss, Jennifer I.
Barjat, Hervé
Emmas, Sally-Ann
Strittmatter, Nicole
Maynard, Juliana
Goodwin, Richard J. A.
Storm, Gert
Lammers, Twan
Puri, Sanyogitta
Ashford, Marianne B.
Barry, Simon T.
High-resolution 3D visualization of nanomedicine distribution in tumors
title High-resolution 3D visualization of nanomedicine distribution in tumors
title_full High-resolution 3D visualization of nanomedicine distribution in tumors
title_fullStr High-resolution 3D visualization of nanomedicine distribution in tumors
title_full_unstemmed High-resolution 3D visualization of nanomedicine distribution in tumors
title_short High-resolution 3D visualization of nanomedicine distribution in tumors
title_sort high-resolution 3d visualization of nanomedicine distribution in tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929971/
https://www.ncbi.nlm.nih.gov/pubmed/31903157
http://dx.doi.org/10.7150/thno.37178
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