Tammy Louise Kalber1, Gavin D. Kenny1,
Nazila Kamaly1,2, Willy Gsell3, Marzena
Wylesinska-Arridge3, Leigh P. Brody1, Andrew D. Miller2,
Jimmy D. Bell1
1Metabolic and Molecular Imaging Group,
Imaging Sciences Department, MRC, Imperial College London, Hammersmith
Hospital, London, United Kingdom; 2Imperial College Genetic
Therapies Centre, Department of Chemistry, Imperial College London, London,
United Kingdom; 3The Biological Imaging Centre, Imperial College
London, London, United Kingdom
Human
colon adenocarcinoma cells, transfected to overexpress inducible nitric oxide
synthase (iNOS) were used to characterize the delivery of iNOS siRNA by
bimodal liposomes in vitro and in vivo. Incubation in vitro resulted in a significant decrease in
nitrite by day 72. Whereas, iNOS overexpressing tumours administered with
iNOS siRNA liposomes resulted in decreased T1 over 24 hours,
consistent with gradual accumulation within the tumour. Tumour volume
measurements showed growth restriction and regression suggestive of siRNA
release resulting in gene silencing and therapeutic effect after ~ 5 days.
However, DCE-MRI was not able to evaluate changes in tumour perfusion
leading.