Combinatorial-designed Hyaluronic Acid Nanoparticles for Tumour Targeted Drug and Small Interfering Ribonucleic Acid Delivery - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 78

1.2 1.2

1
0.8
0.6

a

B16F 10 (65% CD44, highly vascularised)

A549 (>99% CD44, moderate vascularity)

1
0.8
0.6

~55% ~40%

0.4
0.2
0

0.4
0.2
0

HA-PEI/PEG/PLK1 HA-PEI/PEG/PLK1

PBS HA-PEI/PEG/SSB PBS HA-PEI/PEG/SSB

1.2 Hep 3B (~4% CD44, highly vascularised)

1.4

b MDA-MB468 (>99% CD44, poor vascularity)

~15% 1.2

1
0.8
0.6

1
0.8
0.6

~15%

0.4
0.2
0

0.4
0.2
0

PBS HA-PEI/SSB HA-PEI/PLK1

PBS HA-PEI/PEG/PLK1 HA-PEI/PEG/SSB

Figure 3.7 Target gene knockdown in tumours with differential
CD44 expression levels and vascularity. Different types of
subcutaneous tumours (A549, B16F10, Hep3B and MDA-
MB468) with varied levels of CD44 expression and varied levels
of vascularity were used to test the delivery efficiency of the
HA-based nano-systems. Tumors were treated with SSB siRNA
formulated HA-PEI. The SSB gene expression was measured by
qPCR and normalised to either mouse GAPDH or hGAPDH
gene expression, or mouse beta-actin (m-bactin) gene expression.
Adapted from S. Ganesh, A.K. Iyer, D.V. Morrissey and
M.M. Amiji, Biomaterials , 2013, 34 , 3489 [19]

These results together clearly suggested that the CD44 expression
levels may not serve as the only factor for achieving gene silencing
in tumours. Both vascularity and CD44 expression seem to play
an important role in tumour delivery and activity. In other words,
receptors and favourable vascular architecture are crucial to facilitate
tumour selective delivery followed by intracellular uptake and
endosome escape/release to show necessary gene silencing activity.
As Judge and co-workers, and Lee and co-workers reported, the non-