Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. (28th December 2016)

• Record Type: Journal Article
• Authors: Tarassoli, Sam P; de Pinillos Bayona, Alejandra Martinez; Pye, Hayley; Mosse, C Alexander; Callan, John F; MacRobert, Alexander; McHale, Anthony P; Nomikou, Nikolitsa
• Is Part Of: Nanotechnology. Volume 28:Number 5(2017)
• Publication Date: 2016-12-28
• Subjects: indocyanine green -- polyglutamate -- cathepsin B -- near infra-red -- laser cancer treatment; Nanotechnology -- Periodicals; Nanotechnology -- Periodicals; Nanotechnology; Publications périodiques; Nanotechnologies; Periodicals; 620.5
• DOI: 10.1088/1361-6528/28/5/055101
• Languages: English
• ISSNs: 0957-4484

Abstract

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.