Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells

Gennara Cavallaro, Carla Sardo, Gaetano Giammona, Barbara Porsio, Emanuela Fabiola Craparo, Mario Grassi, Francesca Perrone, Barbara Dapas, Gabriele Pozzato, Gabriele Grassi, Rossella Farra

Risultato della ricerca: Article

13 Citazioni (Scopus)

Abstract

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC. The presence of GAL residues in the polyplexes allows the targeting of HCC cells that express the asialo-glycoprotein receptor (ASGP-R). In these cells, but not in ASGP-R non-expressing cells, PHEA-DETA-PEG-GAL/siE2F1 polyplexes induce the reduction of the mRNA and protein levels of E2F1 and of E2F1-regulated genes, all involved in the promotion of the G1/S phase transition. This results in a decrease of cell proliferation with a G1/G0 phase cells accumulation. Notably, removal of GAL residue almost completely abrogates the targeting capacity of the developed polyplexes. In conclusion, the generated polyplexes demonstrate the potential to effectively contributing to the development of novel anti-HCC therapeutic approaches via a siRNA-targeted delivery.
Lingua originaleEnglish
pagine (da-a)397-406
Numero di pagine10
RivistaInternational Journal of Pharmaceutics
Volume525
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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