title: Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.
abstract: Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.
authors.affiliation: Institute of Biological Sciences, Molecular Biology Programme, University of Brasília, Brasília/DF, 70910-900, Brazil.
authors.forename: Ludmilla Regina
authors.initials: LR
authors.lastname: de Souza
authors.forename: Luis Alexandre
authors.initials: LA
authors.lastname: Muehlmann
authors.forename: Lívia Carneiro
authors.initials: LC
authors.lastname: Matos
authors.forename: Rosana
authors.initials: R
authors.lastname: Simón-Vázquez
authors.forename: Zulmira Guerreiro Marques
authors.initials: ZG
authors.lastname: Lacava
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: De-Paula
authors.forename: Ewa
authors.initials: E
authors.lastname: Mosiniewicz-Szablewska
authors.forename: Piotr
authors.initials: P
authors.lastname: Suchocki
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Morais
authors.forename: África
authors.initials: Á
authors.lastname: González-Fernández
authors.forename: Sônia Nair
authors.initials: SN
authors.lastname: Báo
authors.forename: Ricardo Bentes
authors.initials: RB
authors.lastname: Azevedo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000648:ultrastructure; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003165:Complement System Proteins / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D008298:Maleates / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011095:Polyethylenes / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D018036:Selenium Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D008298:Maleates; D053769:Nanocapsules; D011095:Polyethylenes; D018036:Selenium Compounds; C105370:selol; D003165:Complement System Proteins; C043105:poly(methyl vinyl ether-co-maleic anhydride)