Tarassoli, SP;
Martinez de Pinillos Bayona, A;
Pye, H;
Mosse, CA;
Callan, JF;
MacRobert, A;
McHale, AP;
(2017)
Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy.
Nanotechnology
, 28
(5)
, Article 055101. 10.1088/1361-6528/28/5/055101.
![[thumbnail of Nomikou_2017_Nanotechnology_28_055101.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
Nomikou_2017_Nanotechnology_28_055101.pdf - Published Version Download (2MB) |
Abstract
Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.
Archive Staff Only
 |
View Item |
