Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness
Rossella Farra,
Francesco Musiani,
Francesca Perrone,
Maja Čemažar,
Urška Kamenšek,
Federica Tonon,
Michela Abrami,
Aleš Ručigaj,
Mario Grassi,
Gabriele Pozzato,
Deborah Bonazza,
Fabrizio Zanconati,
Giancarlo Forte,
Maguie El Boustani,
Lucia Scarabel,
Marica Garziera,
Concetta Russo Spena,
Lucia De Stefano,
Barbara Salis,
Giuseppe Toffoli,
Flavio Rizzolio,
Gabriele Grassi,
Barbara Dapas
Affiliations
Rossella Farra
Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy
Francesco Musiani
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, I-40127 Bologna, Italy
Francesca Perrone
Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
Maja Čemažar
Department of Experimental Oncology, Institute of Oncology, Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
Urška Kamenšek
Department of Experimental Oncology, Institute of Oncology, Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
Federica Tonon
Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
Michela Abrami
Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy
Aleš Ručigaj
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
Mario Grassi
Department of Engineering and Architecture, University of Trieste, Via Alfonso Valerio, 6/A, I-34127 Trieste, Italy
Gabriele Pozzato
Department of “Scienze Mediche, Chirurgiche e della Salute”, University of Trieste, Cattinara Hospital, Strada di Fiume 447, I-34149 Trieste, Italy
Deborah Bonazza
Department of “Scienze Mediche, Chirurgiche e della Salute”, University of Trieste, Cattinara Hospital, Strada di Fiume 447, I-34149 Trieste, Italy
Fabrizio Zanconati
Department of “Scienze Mediche, Chirurgiche e della Salute”, University of Trieste, Cattinara Hospital, Strada di Fiume 447, I-34149 Trieste, Italy
Giancarlo Forte
Center for Translational Medicine (CTM), International Clinical Research Center (ICRC), St. Anne’s University Hospital, Studenstka 6, 656 91 Brno, Czech Republic
Maguie El Boustani
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Lucia Scarabel
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Marica Garziera
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Concetta Russo Spena
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Lucia De Stefano
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Barbara Salis
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Giuseppe Toffoli
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Flavio Rizzolio
Experimental and Clinical Pharmacology Unit, C.R.O.-National Cancer Institute, via Franco Gallini 2, I-33081 Aviano (PN), Italy
Gabriele Grassi
Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
Barbara Dapas
Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.
