title: Strategies to optimize siRNA delivery to hepatocellular carcinoma cells.
abstract: hepatocellular carcinoma (hcc) is the predominant form of primary liver cancer and the second leading cause of cancer-associated mortality worldwide. available therapies for hcc have limited efficacy due to often late diagnosis and the general resistance of hcc to anti-cancer agents; therefore, the development of novel therapeutics is urgently required. small-interfering rna (sirna) molecules are short, double-stranded rnas that specifically recognize and bind the mrna of a target gene to inhibit gene expression. despite the great therapeutic potential of sirnas towards many human tumors including hcc, their use is limited by suboptimal delivery. Areas covered: In this review, we outline the current data regarding the therapeutic potential of siRNAs in HCC and describe the development of effective siRNA delivery systems. We detail the key problems associated with siRNA delivery and discuss the possible solutions. Finally, we provide examples of the various siRNA delivery strategies that have been employed in animal models of HCC and in human patients enrolled in clinical trials. Expert opinion: Despite the existing difficulties in siRNA delivery for HCC, the increasing scientific attention and breakthrough studies in this field is facilitating the design of novel and efficient technical solutions that may soon find practical applications.
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Scarabel
authors.affiliation: b Department of Life Sciences, Cattinara University Hospital , University of Trieste , Trieste , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Perrone
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Garziera
authors.affiliation: c Department of Engineering and Architecture , University of Trieste , Trieste , Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Farra
authors.affiliation: c Department of Engineering and Architecture , University of Trieste , Trieste , Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.affiliation: d Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Musiani
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Russo Spena
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Salis
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: De Stefano
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.affiliation: a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: c Department of Engineering and Architecture , University of Trieste , Trieste , Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tonon
authors.affiliation: b Department of Life Sciences, Cattinara University Hospital , University of Trieste , Trieste , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Abrami
authors.affiliation: c Department of Engineering and Architecture , University of Trieste , Trieste , Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Chiarappa
authors.affiliation: e Department of 'Scienze Mediche, Chirurgiche e della Salute' , Cattinara University Hospital, University of Trieste , Trieste , Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pozzato
authors.affiliation: f Center for Translational Medicine, International Clinical Research Center , St. Anne's University Hospital , Brno , Czech Republic.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Forte
authors.affiliation: b Department of Life Sciences, Cattinara University Hospital , University of Trieste , Trieste , Italy.|e Department of 'Scienze Mediche, Chirurgiche e della Salute' , Cattinara University Hospital, University of Trieste , Trieste , Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Grassi
authors.affiliation: b Department of Life Sciences, Cattinara University Hospital , University of Trieste , Trieste , Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dapas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D002460:Cell Line; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering
keywords: drug delivery; hepatocellular carcinoma; liposome; polymers; siRNA