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.
- MeSH
- apoptóza MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mannany chemie metabolismus MeSH
- myši inbrední BALB C MeSH
- myši inbrední C3H MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory prsu metabolismus patologie MeSH
- nanočástice aplikace a dávkování chemie MeSH
- optické zobrazování MeSH
- proliferace buněk MeSH
- sentinelová uzlina metabolismus patologie MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We synthesized statistical poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazolines) (POXs) that are molecularly dissolved below their cloud point temperature in aqueous milieu and are incorporated into micellar nanoparticles of biocompatible Pluronic F127 (F127) after heating their solution above transition temperature, T(tr). A functional comonomer 2-(but-3-enyl)-2-oxazoline copolymerized into one of the POXs (polymer E) allows introduction of fenolic moieties and subsequent radionuclide labeling with iodine-125. Self-assembly of the polymer E with F127 leads to formation of radioactive nanoparticles with hydrodynamic diameter 20 nm in aqueous solution by heating to 37 °C. The nanoparticles are intended to be used as radioimaging tool in solid tumor diagnostics.
