title: Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer.
abstract: The design of nanomedicines with suitable physicochemical characteristics for the lymphatic targeting of drugs is critical in order to reach the lymph nodes, where metastatic cells often accumulate. Based on the known effect of particle size and surface hydrophilicity on the capacity of nanocarriers to reach the lymph nodes, here we report the formation and characterization of 100nm polyglutamic acid-polyethylene glycol (PGA-PEG) nanocapsules together with the assessment of their potential for the treatment of cancer with lymphatic metastatic spread. To this purpose, we first studied the biodistribution of fluorescently labeled PGA-PEG nanocapsules (100nm), following, either intravenous or subcutaneous administration. The results confirmed the accumulation of nanocapsules in the lymphatic system, especially upon subcutaneous administration. Next, we evaluated the efficacy and toxicity of the docetaxel-loaded nanocapsules in an orthotopic lung cancer model that metastasizes to the lymph nodes. As expected from the rational design, DCX-loaded PGA-PEG nanocapsules exhibited a greatly enhanced antitumoral efficacy and a reduced toxicity when compared with the commercial formulation Taxotere®. Furthermore, the administration of DCX-loaded PGA-PEG nanocapsules resulted in the practical elimination of the metastatic load in the mediastinal lymph nodes, whereas the treatment with the commercial formulation had a minor effect. Overall, these findings underscore the potential of PGA-PEG nanocapsules for the delivery of anticancer drugs to both, the tumor tissue and the metastatic lymph nodes. Therefore, they represent a promising therapy for the treatment of lung metastatic cancer.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Erea
authors.initials: E
authors.lastname: Borrajo
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Abellan-Pose
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Atenea
authors.initials: A
authors.lastname: Soto
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Fuentes
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Csaba
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain. Electronic address: mariaj.alonso@usc.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15706 Campus Vida, Santiago de Compostela, Spain. Electronic address: anxo.vidal@usc.es.
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000077143:Docetaxel; D000089662:Doublecortin Protein; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology / Q000517:prevention & control*; D016513:Mice, SCID; D053769:Nanocapsules / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D011099:Polyglutamic Acid
keywords: Anti-cancer; Drug delivery; Nanocapsules; Nanomedicine; Nanoparticles; Oncologicals