Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery

Risultato della ricerca: Article

9 Citazioni (Scopus)

Abstract

The advances of short interfering RNA (siRNA)-mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of thepathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA “Inulin COmplex Nanoaggregates”(ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3−5 and selfaggregation triggered by pH increase and physiological salt concentration. INUIMI-DETA showed as well a high buffering capacity in the endosomal pH range of 7.4−5.1. In the concentration range between 25 and 1000 μg/mL INU-IMI-DETA had no cytotoxic effect on breast cancer cells (MCF-7) and no lytic effect onhuman red blood cells. ICONs were prepared by two-step procedure involving complexation and precipitation into DPBS buffer (pH 7.4) to produce siRNA-loaded nanoaggregates with minimized surface charge and suitable size for parenteral administration. Bafilomycin A1 inhibited transfection on MCF-7 cells, indicating that the protonation of the imidazole groups in the endolysosome pathway favors the escape of the system from endolysosomal compartment, increasing the amount of siRNA that can reach the cytoplasm.
Lingua originaleEnglish
pagine (da-a)2352-2366
Numero di pagine15
RivistaBiomacromolecules
Volume17
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Fingerprint Entra nei temi di ricerca di 'Improvements in Rational Design Strategies of Inulin Derivative Polycation for siRNA Delivery'. Insieme formano una fingerprint unica.

  • Cita questo