Biomedical Engineering Reference
In-Depth Information
Figure 5.29
Mean ± SE insulin-mediated glucose uptake in isolated muscle ibres.
Insulin-mediated glucose uptake (measured with luorescent glucose) was markedly
reduced in TRPC3-knockdown ibres (TRPC3 KD). **
P
= 0.01. Reproduced from
Lanner
et al.
99
with permission.
Alternatively, Krajcik
et al.
suggested a non-covalent binding of nucleic acid
to CNTs to eficiently deliver siRNA inside the cells.
101
In their investigation,
aimed to inhibit the extracellular signal-regulated kinases 1 and 2 (ERK1/
ERK2) in order to improve contractile function in reconstituted heart tissue,
the authors used SWCNTs functionalised with hexamethylenediamine
(HMDA) and poly(diallyldimethylammonium) chloride (PDDA) and further
complexed them with unmodiied siRNA. Once inside the cells, the siRNA
sequence was released and induced eficient silencing of target genes (ERK1/
ERK2), showing lower cytotoxic side effects than liposomal transfection.
It is important to notice that siRNA alone was not able to enter the cells,
thus conirming the importance of CNTs as siRNA carriers for a successful
gene therapy of heart failure.
102
In the experiments, ERK1 and ERK2 were
suppressed by nearly 80%, while maximum silencing results were achieved
with a 1:1 PDDA-SWCNT mixture.
It has been also shown that the delivery of siRNA to human T cells to
silence the expression of the human immunodeiciency virus (HIV)-speciic
cell-surface receptors CD4 and/or co-receptors CXCR4/CCR5 can block HIV
entry and thus reduce infection.
103-105
However, certain cells are still dificult
to transfect by non-viral agents, as in the case of liposomes that have been
shown to be incapable of siRNA delivery into T cells.
103
On the contrary, Dai
et al.
demonstrated that SWCNTs were capable of siRNA delivery to afford
eficient RNA interference of CXCR4 and CD4 receptors on human T cells
through the use of functionalised CNTs.
106
CNTs were initially solubilised
through non-covalent adsorption of phospholipids (PLs) and coupled with
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