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Volume 4
Nano Research & Applications
ISSN: 2471-9838
Page 67
JOINT EVENT
August 16-18, 2018 | Dublin, Ireland
&
12
th
Edition of International Conference on
Nanopharmaceutics and Advanced Drug Delivery
25
th
Nano Congress for
Future Advancements
Nano Congress 2018
&
Nano Drug Delivery 2018
August 16-18, 2018
Phosphonium carbosilane dendrimers: Efficient non-viral vectors for siRNA delivery to
adenocarcinoma cells
in vitro
Regina Herma
University of Jan Evangelista Purkyna, Czech Republic
G
ene therapy is a rapidly growing field of biomedical research which has sparked great interest because it offers the possibility
of a permanent cure a variety of genetic-based diseases. The success of gene therapy depends on the development of
suitable vectors for the delivery nucleic acids into cells. Our work is focused on the comparative study of the two types of
cationic carbosilane dendrimers terminated with the ammonium and phosphonium groups for their use as non-viral vectors
for siRNA transfection. We present a part of work devoted to characterization of dendriplexes formed from generation
1-3 (G1-3) of carbosilane dendrimers and model siRNA. We used a number of biophysical methods (e.g. Gel retardation
electrophoresis, DLS, ξ (zeta)-potential, AFM) for characterization of dendriplexes. Transfection efficiency was evaluated by
Fluorescence Microscopy and Flow Cytometry. Both types of dendrimers G2-G3 form stable complexes with siRNA due to
positive charge of surface groups of dendrimers and negative charge of siRNA backbone. Formation of dendriplexes was
investigated at different charge ratio (1/5 – 10/1 (+/-)) to find the optimal properties of complexes (e.g. stability, surface charge,
dimensions) for transfection of cells.
In vitro
transfection experiments proved the ability of both G3 dendriplex structures to
enter the cells, with maximal achieved transfection efficiency at 7/1 (+/-) charge ratio. Ammonium dendrimers achieved max.
30% of transfected cells. More than 70% of cells were transfected under the same conditions with phosphonium terminated
dendrimers. With the aim to optimize the properties of phosphoniumdendriplexes we incorporated new periphery substituents
(P(Et
2
)
2
(CH
2
)
3
OH, P(Ph)
3
, P(C
6
H
4
-OMe)
3
, PBu
3
) into dendrimer structure. Similar cytotoxicity (except PBu3) and transfection
efficiencies were obtained with the exception of P(Ph)3 peripheral substituent. This type of dendrimer exhibits more than
80% transfection efficiency and seems to be the “hot” candidate for further improvements of gene delivery by phosphonium
carbosilane dendrimer vectors
Recent Publications
1. Strasak T et al. (2017) Phosphonium carbosilane dendrimers for biomedical applications: synthesis, characterization
and cytotoxicity evaluation. RSC Advances. 7(30):18724-18744.
2. Ferenc M et al. (2013) Phosphorus dendrimers as carriers of siRNA: characterisation of dendriplexes. Molecules.
18(12):4451-4466.
3. Biswas S and Torchilin V (2013) Dendrimers for siRNA Delivery. Pharmaceuticals. 6(12):161-183.
4. Dufes C, Uchegbu I and Schatzlein A (2005) Dendrimers in gene delivery. Advanced Drug Delivery Reviews.
57(15):2177-2202.
5. Biricova V and Laznickova A (2009) Dendrimers: analytical characterization and applications. Bioorganic Chemistry.
37(6):185-192.
Biography
Regina Herma is PhD candidate at Jan Evangelista Purkyne University(UJEP),Czech Republic. Her work is mainly focused on the effect of type, generation and
surface modification of carbosilane dendrimers on the interaction with selected nucleic acids for applications in biomedicine (transport molecules for drug targeting,
vectors for gene therapy, potential treatment of lung cancer). She is part of a research team for a number of projects.
hermaregina@gmail.comRegina Herma, Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-015