title: Carotenoid Nanovector for Efficient Therapeutic Gene Knockdown of Transcription Factor FOXC1 in Liver Cancer.
abstract: Transcription factor FOXC1 has been implicated to play a critical role in hepatocellular carcinoma (HCC) progression, but targeting FOXC1 for therapeutic benefit remains a challenge owing to its location inside the cell nucleus. Herein we report successful therapeutic gene knockdown of transcription factor FOXC1 in liver cancer cells through efficient delivery of siFOXC1 using novel carotenoid functionalized dendritic nanoparticles (CDN). This delivery system also displayed a markedly reduced toxicity profile compared to a standard siRNA transfection agent. We were able to achieve ∼90% FOXC1 knockdown using the CDN-siFOXC1 complex. Additionally, it was found to have ∼18% greater delivery efficiency compared to treatments with particles which have no carotenoid tagging, thereby emphasizing the role of carotenoid mediated cell internalization in the efficient delivery of CDN-siFOXC1 complex in liver cancer cells.
authors.affiliation: Department of Bioengineering and Beckman Institute, Materials Science and Engineering, University of Illinois at Urbana-Champaign and Carle Cancer Center , 502 North Busey, Urbana, Illinois 61801, United States.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Misra
authors.affiliation: Department of Surgery, University of Illinois College of Medicine, Division of Surgical Oncology, Carle Cancer Center , 509 West University Avenue, Urbana, Illinois 61801, United States.
authors.forename: Tania
authors.initials: T
authors.lastname: Ray
authors.affiliation: Department of Bioengineering and Beckman Institute, Materials Science and Engineering, University of Illinois at Urbana-Champaign and Carle Cancer Center , 502 North Busey, Urbana, Illinois 61801, United States.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ostadhossein
authors.affiliation: Department of Surgery, University of Illinois College of Medicine, Division of Surgical Oncology, Carle Cancer Center , 509 West University Avenue, Urbana, Illinois 61801, United States.
authors.forename: Bomy
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Illinois College of Medicine, Division of Surgical Oncology, Carle Cancer Center , 509 West University Avenue, Urbana, Illinois 61801, United States.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Ray
authors.affiliation: Department of Bioengineering and Beckman Institute, Materials Science and Engineering, University of Illinois at Urbana-Champaign and Carle Cancer Center , 502 North Busey, Urbana, Illinois 61801, United States.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D002338:Carotenoids / Q000008:administration & dosage*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D002338:Carotenoids