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.

C R O National Cancer Institute via Franco Gallini 2 1 33081 Aviano Italy

Center for Translational Medicine St Anne's University Hospital Studenstka 6 656 91 Brno Czech Republic

Department of Engineering and Architecture University of Trieste Via Alfonso Valerio 6 A 1 34127 Trieste Italy

Department of Experimental Oncology Institute of Oncology Ljubljana Zaloska 2 SI 1000 Ljubljana Slovenia

Department of Life Sciences Cattinara University Hospital Trieste University Strada di Fiume 447 1 34149 Trieste Italy

Department of Molecular Sciences and Nanosystems Ca' Foscari University via Torino 155 1 30172 Mestre Italy

Department of Scienze Mediche Chirurgiche e della Salute University of Trieste Cattinara Hospital Strada di Fiume 447 1 34149 Trieste Italy

Doctoral School in Chemistry University of Trieste 34100 Trieste Italy

Doctoral School in Molecular Biomedicine University of Trieste 34100 Trieste Italy

Experimental and Clinical Pharmacology Unit C R O National Cancer Institute via Franco Gallini 2 1 33081 Aviano Italy

Faculty of Chemistry and Chemical Technology University of Ljubljana Večna pot 113 SI 1000 Ljubljana Slovenia

Faculty of Health Sciences University of Primorska Polje 42 SI 6310 Izola Slovenia

Laboratory of Bioinorganic Chemistry Department of Pharmacy and Biotechnology University of Bologna 1 40127 Bologna Italy

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