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Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

Tarassoli, Sam P, Martinez de Pinillos Bayona, Alejandra, Pye, Hayley, Mosse, C. Alexander, Callan, J, MacRobert, Alexander, McHale, AP and Nomikou, Nikolitsa (2017) Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. Nanotechnology, 28 (5). [Journal article]

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DOI: doi: 10.1088/1361-6528/28/5/055101

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.

Item Type:Journal article
Keywords:indocyanine green, polyglutamate, cathepsin B, near infra-red, laser cancer treatment
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:37090
Deposited By: Professor Anthony McHale
Deposited On:06 Mar 2017 08:55
Last Modified:06 Mar 2017 08:55

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