Combinatorial-designed Hyaluronic Acid Nanoparticles for Tumour Targeted Drug and Small Interfering Ribonucleic Acid Delivery - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 83

After two rounds of cisplatin and siRNA treatments, (three siRNA
doses and one cisplatin dose), the groups that had combination
treatment (survivin+cisplatin, bcl-2+cisplatin or survivin + bcl-
2+cisplatin) showed significantly better tumour growth inhibition
compared to the PBS or CTL group and the groups that had single
agent treatment (survivin , bcl-2 or cisplatin) with growth inhibition
of 62% for the survivin + bcl-2+cisplatin group, 58% for the bcl-
2+cisplatin group and 52% for the survivin+cisplatin group. There
was a slight added benefit of knocking down both survivin and bcl-2
expression levels together with cisplatin treatment over either of the
siRNA+ cisplatin treatments in this study (62% growth inhibition
versus 58 or 52% growth inhibition) supporting the pattern that was
found in in vitro study results (80% killing versus approximately
72% killing). The tumour growth inhibition in mice that had only
cisplatin treatment was 31% and it was 29% for mice that had CTL
siRNA+cisplatin treatment. The siRNA treatment groups such as
survivin alone, bcl-2 alone and survivin+bcl-2 groups had 31, 31
and 30% growth inhibition respectively. The control group with no
cisplatin showed almost no difference in tumour growth from the PBS
treated group. Altogether our data suggested that the combination
of survivin or bcl-2 or survivin+bcl-2 down-regulation and cisplatin
treatment together demonstrated a combination or synergistic effect
[22]. Again, the study results suggested that the combination of
anticancer drug with suppression of non-pump resistance seems to
be required for effective killing of MDR cells. In addition, it was
also learned that these treatments were well-tolerated by these mice
with resistant tumours as indicated by no weight loss or no elevation
of liver enzyme levels during the study period. Taken together, our
findings provide strong evidence that the siRNA encapsulated HA
nanoparticles provide safe and sequence specific silencing of resistance
related genes and reverse of resistance and thus mediate significantly
better efficacy in combination with cisplatin treatment.
3.6 Conclusions
In addition to several other groups, we have evaluated a series of