title: Anti-tumor efficacy of chitosan-g-poly(ethylene glycol) nanocapsules containing docetaxel: anti-TMEFF-2 functionalized nanocapsules vs. non-functionalized nanocapsules.
abstract: The development and evaluation of PEGylated chitosan (CS) nanocapsules (NCs) conjugated to a monoclonal antibody anti-TMEFF-2 (CS-PEG-anti-TMEFF-2 mAb NCs) for targeted delivery of docetaxel (DCX) is presented. CS-PEG-Biotin NCs, displaying biotin tags at their surface, were obtained and efficiently functionalized with an anti-TMEFF-2 mAb through a convenient avidin-biotin approach. Cell cycle analysis after treatment with different DCX-loaded CS-PEG NC formulations indicated that the encapsulated drug remained fully active, showing a similar functional behavior to free DCX. In vivo efficacy studies using a non-small cell lung carcinoma xenograft revealed that CS-PEG-anti-TMEFF-2 NCs resulted as effective as free DCX (Taxotere®). Interestingly, differences on the pharmacodynamic behavior among the different DCX formulations were observed. Thus, while free DCX exhibited a fast and short effect on tumor volume reduction, CS-PEG-anti-TMEFF-2 mAb NCs showed a delayed and prolonged action, with no significant side effects of treatments.
authors.affiliation: Department of Physiology, Faculty of Medicine, Institute of Health Research, University of Santiago de Compostela 15782, Santiago de Compostela, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Torrecilla
authors.forename: Maria V
authors.initials: MV
authors.lastname: Lozano
authors.forename: Enrique
authors.initials: E
authors.lastname: Lallana
authors.forename: Jose I
authors.initials: JI
authors.lastname: Neissa
authors.forename: Ramon
authors.initials: R
authors.lastname: Novoa-Carballal
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Megia
authors.forename: Dolores
authors.initials: D
authors.lastname: Torres
authors.forename: Ricardo
authors.initials: R
authors.lastname: Riguera
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Alonso
authors.forename: Fernando
authors.initials: F
authors.lastname: Dominguez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D000077143:Docetaxel; D000089662:Doublecortin Protein; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D016513:Mice, SCID; D053769:Nanocapsules; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D011092:Polyethylene Glycols / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D008565:Membrane Proteins; D053769:Nanocapsules; D009363:Neoplasm Proteins; C423567:TMEFF2 protein, human; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D048271:Chitosan