title: Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles.
abstract: Small interfering RNA (siRNA) molecules specifically target messenger RNA species, decreasing intracellular protein levels. β-Catenin protein concentrations are increased in 70-80% of colon tumors, promoting tumor progression. Chitosan exhibits low levels of toxicity and can be transported across mucosal membranes; therefore, our objective was to develop chitosan and poly(ethylene glycol)-grafted (PEGylated) chitosan nanoparticles, 100-150nm in diameter, encapsulating anti-β-catenin siRNA for transfection into colon cancer cells. Encapsulation efficiencies up to 97% were observed. Confocal microscopy visualized the entry of fluorescently-tagged siRNA into cells. Western blot analysis showed that both chitosan and PEGylated chitosan nanoparticles containing anti-β-catenin siRNA decreased β-catenin protein levels in cultured colon cancer cells. These results indicate that nanoparticles made with chitosan and PEGylated chitosan can successfully enter colon cancer cells and decrease the level of a protein that promotes tumor progression. These or similar nanoparticles may prove beneficial for the treatment of colon cancer in humans.
authors.affiliation: Texas State University, Department of Chemistry and Biochemistry, San Marcos, TX 78666, USA. Electronic address: WR01@txstate.edu.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Rudzinski
authors.affiliation: Texas State University, Department of Chemistry and Biochemistry, San Marcos, TX 78666, USA. Electronic address: Adriana.S.Palacios@ttuhsc.edu.
authors.forename: Adriana
authors.initials: A
authors.lastname: Palacios
authors.affiliation: Texas State University, Department of Chemistry and Biochemistry, San Marcos, TX 78666, USA. Electronic address: abuzarahmed01@gmail.com.
authors.forename: Abuzar
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Texas State University, School of Family and Consumer Sciences, Nutrition and Foods Program, San Marcos, TX 78666, USA. Electronic address: ML48@txstate.edu.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lane
authors.affiliation: Soniya College of Pharmacy, Dharwad 580 002, India. Electronic address: aminabhavit@gmail.com.
authors.forename: Tejraj M
authors.initials: TM
authors.lastname: Aminabhavi
mesh_terms: D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D048271:Chitosan
keywords: Chitosan; Chitosan (PubChem CID 71853); Colon cancer; Nanoparticles; PEGylated chitosan; Small interfering RNA; Sodium triphosphate pentabasic (PubChem CID 24455); β-Catenin