Biomedical Engineering Reference
In-Depth Information
3.4.2 Choice of Tumour Models for Hyaluronic Acid-based
Nanoparticle Delivery
In addition to demonstrating receptor-mediated delivery and gene
silencing in cells, the siRNA encapsulated modified HA derivatives
also showed target-specific activity in solid tumours. Choi and
co-workers systemically injected their Cy5.5-labelled HA NP with
different sizes into mice bearing SCC tumours [7]. Irrespective of the
particle sizes, these NP circulated in the blood stream for 2 days and
selectively accumulated in the tumour site. They also showed with
their non-invasive near infrared fluorescence imaging system that the
smaller particles reached the tumours more efficiently than the larger
particles. In addition to this, they also nicely demonstrated that the
concentration of HA-NP dramatically reduced when mice were pre-
treated with excess of free HA. In addition, this research group also
evaluated the PEG-modified HA particles for tumour delivery with
the aim of improving the half-life of the particles and thus resulting in
enhanced tumour targeting [18]. Using these PEG-modified HA-NP,
they demonstrated that they could effectively reduce the liver uptake
and increase their circulation time in the blood of tumour bearing
mice. They also showed that these particles accumulated 1.6-fold
higher than the non-modified HA-NP.
Jiang and co-workers also showed that the HA-PEI/siRNA complex
accumulated mainly in tissues with high levels of HA receptors such
as liver, kidney and tumour. Furthermore, they also showed that the
intratumoural injection of anti-vascular endothelial growth factor
targeted siRNA/HA-PEI complex resulted in effective inhibition of
tumour growth by the CD44-mediated endocytosis to tumour cells
in C57BL/6 mice [21].
Similar to what Choi and colleagues did, to increase the circulation
time of the HA nanoparticles
in vivo
, we used PEG-modified HA
blocks along with the HA-PEI derivative when tested in tumour
bearing mice. When HA-PEI/HA-PEG/siRNA particles were dosed
at 0.5 mg/kg every day for 3 days, we observed approximately 50%
target knockdown in CD44 overexpressing A549 tumours but
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