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
• 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

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as "stealth" coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.

• Publication type
• Journal Article MeSH