title: Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate) nanoparticles.
abstract: Doxorubicin (Dox) is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate) (PBCA). The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP) matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic) drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations). Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug's antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma.
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Biosanitary Institute of Granada (IBS Granada), SAS Universidad de Granada, Granada, Spain.
authors.forename: Consolación
authors.initials: C
authors.lastname: Melguizo
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Cabeza
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Biosanitary Institute of Granada (IBS Granada), SAS Universidad de Granada, Granada, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Prados
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Department of Health Science, University of Jaén, Jaén, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Department of Health Science, University of Jaén, Jaén, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Caba
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Department of Health Science, University of Jaén, Jaén, Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Rama
authors.affiliation: Department of Applied Physics, University of Granada, Granada, Spain.
authors.forename: Ángel V
authors.initials: ÁV
authors.lastname: Delgado
authors.affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center, SAS Universidad de Granada, Granada, Spain ; Biosanitary Institute of Granada (IBS Granada), SAS Universidad de Granada, Granada, Spain ; Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Arias
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004659:Enbucrilate / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004317:Doxorubicin; D004659:Enbucrilate
keywords: PBCA; cancer chemotherapy; drug carrier; lung cancer; polymeric nanoparticles