Chemistry Reference
In-Depth Information
Fig. 8.3
(
a
) Real-time images of fluorescent dye-loaded HA-ceramide nanoparticles accumulated
into the MCF-7/ADR xenograft tumor. Pictures in the superior part of the panel are mice treated
only with nanoparticles. Pictures in the inferior part of the panel are animals treated with HA
before the injection of HA-ceramide nanoparticles. (
b
) Quantitative evaluation of fluorescence
until 24 h (Reproduced with permission, copyright 2011 Elsevier [
56
])
tissue fibrosis in general and in particular liver fibrosis. Successful targeting of
siRNA needs the development of an appropriate carrier, which should complex
plasmid and allow accumulation into the target organ. Complexes plasmids/
polymers are an advantageous alternative to the employ of attenuated viruses.
Polyethyleneimine (PEI) is still the more efficient polymer in terms of complex
formation and transfection efficiency even if the toxicity limits its employ. Grafting
of PEI into HA can mask PEI toxicity, improving polyplex plasma half-life. Thiol
cross-linked PEI derivative (PEISS) was grafted into HA through an EDC/HOBT
activation of the glucuronic COOH groups (see Scheme
8.4
for general reaction
procedure). Copolymer HA-g-PEISS complexed siRNA with a weight ratio poly-
mer/RNA equal to 10 forming aggregates with a mean diameter of 140 nm and a
slightly positive zeta potential. First, in vitro silencing effect was tested using
luciferase siRNA, and testing transfection efficiency in CD44-expressing cells
