title: Electroporation and lipid nanoparticles with cyanine IR-780 and flavonoids as efficient vectors to enhanced drug delivery in colon cancer.
abstract: Nanocarriers and electroporation (also named electropermeabilization) are convenient methods to increase drug transport. In the current study, we present an effective support of drug delivery into cancer cells, utilizing these methods. We compare the efficiency of each of them and their combination. Multifunctional solid lipid nanoparticles (SLNs) loaded with a cyanine-type IR-780 - acting as a diagnostic agent and a photosensitizer, and a flavonoid derivative - baicalein (BAI) or fisetin (FIS) as a therapeutic cargo - were fabricated via solvent-diffusion method. A therapy supplemented with flavonoids may provide a more precise method to apply desirable lower drug doses and is more likely to result in lower toxicity and a decrease in tumor growth. The SLNs were stabilized with Phospholipon 90G at various concentrations; cetyl palmitate (CP) was applied as a solid matrix. The obtained nanosystems were characterized by dynamic light scattering (size along with size distribution), UV-vis (cargos encapsulation efficiency) and atomic force microscopy (morphology and shape). The obtained SLNs were used as drug carriers alone and in combination with electropermeabilization induced by millisecond pulsed electric fields of high intensity. Two cell lines were selected for the study: LoVo and CHO-K1. The viability was assessed after electroporation alone, the use of electroporation and nanoparticles, and nanoparticles or drugs alone. The intracellular accumulation of cyanine IR-780 and the impact on intracellular structure organization of cytoskeleton was visualized with confocal microscopy method with alpha-actin and beta-tubulin. In this study, the efficacy of nanoparticles with mixed cargo, additionally enhanced by electroporation, is demonstrated to act as an anticancer modality to eliminate cancer cells.
authors.affiliation: Department of Medical Biochemistry, Medical University, Chalubinskiego 10 St., 50-368 Wrocław, Poland. Electronic address: julita.kulbacka@umed.wroc.pl.
authors.forename: Julita
authors.initials: J
authors.lastname: Kulbacka
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Pucek
authors.affiliation: Department of Biomedical Engineering, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kotulska
authors.affiliation: Department of General Zoology, Zoological Institute, University of Wrocław, Sienkiewicza 21 St., 50-335 Wrocław.
authors.forename: Magda
authors.initials: M
authors.lastname: Dubińska-Magiera
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rossowska
authors.affiliation: CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne BP64182, F-31077 Toulouse, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Rols
authors.affiliation: Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Kazimiera Anna
authors.initials: KA
authors.lastname: Wilk
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003412:Cricetulus; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004337:Drug Carriers / Q000737:chemistry*; D018274:Electroporation; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D044948:Flavonols; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010168:Palmitates / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D004337:Drug Carriers; D044950:Flavanones; D005419:Flavonoids; D044948:Flavonols; D007211:Indoles; D010168:Palmitates; D017319:Photosensitizing Agents; D016159:Tumor Suppressor Protein p53; C006680:baicalein; C006957:cetyl palmitate; D013482:Superoxide Dismutase; C017875:fisetin
keywords: Electroporation; Flavonoids; Photodynamic reaction; Solid lipid nanoparticles