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Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors
M. Jirátová, A. Gálisová, M. Rabyk, E. Sticová, M. Hrubý, D. Jirák
Language English Country Switzerland
Document type Journal Article
Grant support
16-30544a
the Grant Agency of the Ministry of Health
IN00023001
MH CR-DRO
18-07983S
the Czech Science Foundation
282216
the Charles University Grant Agency
NLK
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- MeSH
- Apoptosis MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Mannans chemistry metabolism MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C3H MeSH
- Mice, Nude MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Breast Neoplasms metabolism pathology MeSH
- Nanoparticles administration & dosage chemistry MeSH
- Optical Imaging MeSH
- Cell Proliferation MeSH
- Sentinel Lymph Node metabolism pathology MeSH
- Xenograft Model Antitumor Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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.
Department of Physiology Faculty of Science Charles University 128 00 Prague Czech Republic
Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic
Institute of Macromolecular Chemistry Czech Academy of Sciences 162 00 Prague Czech Republic
References provided by Crossref.org
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