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Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip

[Image: see text] The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelia...

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Autores principales: Feiner-Gracia, Natalia, Glinkowska Mares, Adrianna, Buzhor, Marina, Rodriguez-Trujillo, Romen, Samitier Marti, Josep, Amir, Roey J., Pujals, Silvia, Albertazzi, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818510/
https://www.ncbi.nlm.nih.gov/pubmed/33490884
http://dx.doi.org/10.1021/acsabm.0c01209
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author Feiner-Gracia, Natalia
Glinkowska Mares, Adrianna
Buzhor, Marina
Rodriguez-Trujillo, Romen
Samitier Marti, Josep
Amir, Roey J.
Pujals, Silvia
Albertazzi, Lorenzo
author_facet Feiner-Gracia, Natalia
Glinkowska Mares, Adrianna
Buzhor, Marina
Rodriguez-Trujillo, Romen
Samitier Marti, Josep
Amir, Roey J.
Pujals, Silvia
Albertazzi, Lorenzo
author_sort Feiner-Gracia, Natalia
collection PubMed
description [Image: see text] The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix, and eventually cancer cell membrane. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is the key factor for the rational design of these systems. One of the main challenges is that current 2D in vitro models do not provide exhaustive information, as they fail to recapitulate the 3D tumor microenvironment. This deficiency in the 2D model complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic cancer-on-a-chip. The combination of advanced imaging and a reliable 3D model allows tracking of micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation continuously followed by spectral imaging during the crossing of barriers, revealing the interplay between carrier structure, micellar stability, and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip resulted in the establishment of a robust testing platform suitable for real-time imaging and evaluation of supramolecular drug delivery carrier’s stability.
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spelling pubmed-78185102021-01-22 Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip Feiner-Gracia, Natalia Glinkowska Mares, Adrianna Buzhor, Marina Rodriguez-Trujillo, Romen Samitier Marti, Josep Amir, Roey J. Pujals, Silvia Albertazzi, Lorenzo ACS Appl Bio Mater [Image: see text] The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix, and eventually cancer cell membrane. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is the key factor for the rational design of these systems. One of the main challenges is that current 2D in vitro models do not provide exhaustive information, as they fail to recapitulate the 3D tumor microenvironment. This deficiency in the 2D model complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic cancer-on-a-chip. The combination of advanced imaging and a reliable 3D model allows tracking of micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation continuously followed by spectral imaging during the crossing of barriers, revealing the interplay between carrier structure, micellar stability, and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip resulted in the establishment of a robust testing platform suitable for real-time imaging and evaluation of supramolecular drug delivery carrier’s stability. American Chemical Society 2020-12-23 2021-01-18 /pmc/articles/PMC7818510/ /pubmed/33490884 http://dx.doi.org/10.1021/acsabm.0c01209 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Feiner-Gracia, Natalia
Glinkowska Mares, Adrianna
Buzhor, Marina
Rodriguez-Trujillo, Romen
Samitier Marti, Josep
Amir, Roey J.
Pujals, Silvia
Albertazzi, Lorenzo
Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title_full Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title_fullStr Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title_full_unstemmed Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title_short Real-Time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-Chip
title_sort real-time ratiometric imaging of micelles assembly state in a microfluidic cancer-on-a-chip
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818510/
https://www.ncbi.nlm.nih.gov/pubmed/33490884
http://dx.doi.org/10.1021/acsabm.0c01209
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