Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction.

Abstract:

:This paper examines a perspective on the use of newly engineered nanomaterials as effective and safe carriers of genes for the therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus and carbosilane) were complexed with anticancer siRNA and their biophysical properties of the dendriplexes analyzed. The potential of the dendrimers as nanocarriers for anticancer siBcl-xl, siBcl-2, siMcl-1 siRNAs and a siScrambled sequence was explored. Dendrimer/siRNA complexes were characterized by methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. Some of the experiments were done with heparin to check if siRNA can be easily disassociated from the complexes, and whether released siRNA maintains its structure after interaction with the dendrimer. The results indicate that siRNAs form complexes with all the dendrimers tested. Oligoribonucleotide duplexes can be released from dendriplexes after heparin treatment and the structure of siRNA is maintained in the case of PAMAM or carbosilane dendrimers. The dendrimers were also effective in protecting siRNA from RNase A activity. The selection of the best siRNA carrier will be made based on cell culture studies (Part B).

journal_name

Int J Pharm

authors

Ionov M,Lazniewska J,Dzmitruk V,Halets I,Loznikova S,Novopashina D,Apartsin E,Krasheninina O,Venyaminova A,Milowska K,Nowacka O,Gomez-Ramirez R,de la Mata FJ,Majoral JP,Shcharbin D,Bryszewska M

doi

10.1016/j.ijpharm.2015.03.024

subject

Has Abstract

pub_date

2015-05-15 00:00:00

pages

261-9

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(15)00240-9

journal_volume

485

pub_type

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