title: Selective interaction of PEGylated polyglutamic acid nanocapsules with cancer cells in a 3D model of a metastatic lymph node.
abstract: BACKGROUND
  Metastases are the most common reason of cancer death in patients with solid tumors. Lymph nodes, once invaded by tumor cells, act as reservoirs before cancer cells spread to distant organs. To address the limited access of intravenously infused chemotherapeutics to the lymph nodes, we have developed PEGylated polyglutamic acid nanocapsules (PGA-PEG NCs), which have shown ability to reach and to accumulate in the lymphatic nodes and could therefore act as nanotransporters. Once in the lymphatics, the idea is that these nanocapsules would selectively interact with cancer cells, while avoiding non-specific interactions with immune cells and the appearance of subsequent immunotoxicity.
  
  
  RESULTS
  The potential of the PGA-PEG NCs, with a mean size of 100 nm and a negative zeta potential, to selectively reach metastatic cancer cells, has been explored in a novel 3D model that mimics an infiltrated lymph node. Our 3D model, a co-culture of cancer cells and lymphocytes, allows performing experiments under dynamic conditions that simulate the lymphatic flow. After perfusion of the nanocarriers, we observe a selective interaction with the tumor cells. Efficacy studies manifest the need to develop specific therapies addressed to treat metastatic cells that can be in a dormant state.
  
  
  CONCLUSIONS
  We provide evidence of the ability of PGA-PEG NCs to selectively interact with the tumor cells in presence of lymphocytes, highlighting their potential in cancer therapeutics. We also state the importance of designing precise in vitro models that allow performing mechanistic assays, to efficiently develop and evaluate specific therapies to confront the formation of metastasis.
authors.affiliation: Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital/SERGAS, Santiago de Compostela, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Alonso-Nocelo
authors.affiliation: Nanobiofar Group, Center for Research in Molecular and Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Abellan-Pose
authors.affiliation: Cell Cycle and Oncology Group CiCLOn, IDIS, Center for Research in Molecular and Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital/SERGAS, Santiago de Compostela, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.affiliation: Nanobiofar Group, Center for Research in Molecular and Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Csaba
authors.affiliation: Nanobiofar Group, Center for Research in Molecular and Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital/SERGAS, Santiago de Compostela, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lopez-Lopez
authors.affiliation: Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital/SERGAS, Santiago de Compostela, Spain. maria.de.la.fuente.freire@sergas.es.
authors.forename: Maria
authors.initials: M
authors.lastname: de la Fuente
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002232:Carbocyanines / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D018920:Coculture Techniques; D000077143:Docetaxel; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008954:Models, Biological; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D012212:Rheology; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002232:Carbocyanines; D005456:Fluorescent Dyes; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols
keywords: 3D cell culture; Lymph nodes; Metastasis; Nanocapsules; Perfusion