Biomedical Engineering Reference
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targeted liposomal stable nucleic acid lipid particles carrying siRNA
efficiently delivered siRNA to highly vascularised Hep3B tumours
and other liver tumours that are highly vascularised mainly by the
enhanced permeability retention (EPR) effect [32, 33]. However, these
non-targeted systems completely failed to deliver siRNA to tumours
that are not vascularised enough (unpublished data), indicating
that targeting may be necessary to penetrate hypovascular or solid
tumours. In selection of the ideal candidate tumours, obviously the
ones with higher levels of CD44 (that promotes receptor-mediated
internalisation) and higher levels of vascularity that facilitate tumour
accumulation based on the EPR effect will show pronounced effect
of activity.
To check the activity of cisplatin encapsulated HA-ODA nanoparticles,
with and without PEG, we used the same resistant A549
DDP
tumours
as previously. Mice treated with either cisplatin or HA-ODA/
cisplatin or HA-ODA/PEG/cisplatin nanoparticles showed tumour
growth inhibition compared to the PBS treated group. In addition
to showing slightly better efficacy compared to the other two at the
early time points, the HA-ODA/cisplatin system also demonstrated
some favourable safety properties compared to the other two, thus
it was selected for the combination efficacy study [23].
3.5 Applications of Hyaluronic Acid Nanoparticles in
Reversing Tumour Multidrug Resistance
3.5.1 Establishment of Drug Resistant Tumour Models
Since our group was interested in reversing the resistance in lung
tumours, we chose a pair of resistant/sensitive NSCLC and SCLC cell
lines and identified the genes that were overexpressed in the resistant
cells compared to their companion sensitive cell lines [23]. Using
the appropriate set of primers and by running reverse transcription
polymerase chain reaction, we identified two overexpressed pump
mediated (mdr-1, mrp-1) and two overexpressed non-pump mediated
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