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.
- indocyanine green
- cathepsin B
- near infra-red
- laser cancer treatment
Tarassoli, S. P., Martinez de Pinillos Bayona, A., Pye, H., Mosse, C. A., Callan, J., MacRobert, A., McHale, AP., & Nomikou, N. (2017). Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. Nanotechnology, 28(5), . https://doi.org/10.1088/1361-6528/28/5/055101