Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors

Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an...

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Main Authors: Markéta Jirátová, Andrea Gálisová, Maria Rabyk, Eva Sticová, Martin Hrubý, Daniel Jirák
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/1/146
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author Markéta Jirátová
Andrea Gálisová
Maria Rabyk
Eva Sticová
Martin Hrubý
Daniel Jirák
author_facet Markéta Jirátová
Andrea Gálisová
Maria Rabyk
Eva Sticová
Martin Hrubý
Daniel Jirák
author_sort Markéta Jirátová
collection DOAJ
description Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.
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spelling doaj.art-0daf0ee8e4dd4534bf800e4ff12a85492023-11-21T07:25:51ZengMDPI AGMolecules1420-30492020-12-0126114610.3390/molecules26010146Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and TumorsMarkéta Jirátová0Andrea Gálisová1Maria Rabyk2Eva Sticová3Martin Hrubý4Daniel Jirák5Institute for Clinical and Experimental Medicine (IKEM), 140 21 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine (IKEM), 140 21 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, 162 00 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine (IKEM), 140 21 Prague, Czech RepublicInstitute of Macromolecular Chemistry, Czech Academy of Sciences, 162 00 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine (IKEM), 140 21 Prague, Czech RepublicEarly detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.https://www.mdpi.com/1420-3049/26/1/146mannanSLNcancermultimodality imaging4T1 cellsMRI
spellingShingle Markéta Jirátová
Andrea Gálisová
Maria Rabyk
Eva Sticová
Martin Hrubý
Daniel Jirák
Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
Molecules
mannan
SLN
cancer
multimodality imaging
4T1 cells
MRI
title Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
title_full Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
title_fullStr Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
title_full_unstemmed Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
title_short Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
title_sort mannan based nanodiagnostic agents for targeting sentinel lymph nodes and tumors
topic mannan
SLN
cancer
multimodality imaging
4T1 cells
MRI
url https://www.mdpi.com/1420-3049/26/1/146
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