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

Sam P Tarassoli, Alejandra Martinez de Pinillos Bayona, Hayley Pye, C. Alexander Mosse, J Callan, Alexander MacRobert, AP McHale, Nikolitsa Nomikou

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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.
Original languageEnglish
JournalNanotechnology
Volume28
Issue number5
Early online date28 Dec 2016
DOIs
Publication statusPublished - 3 Feb 2017

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Keywords

  • indocyanine green
  • polyglutamate
  • cathepsin B
  • near infra-red
  • laser cancer treatment

Cite this

Tarassoli, S. P., Martinez de Pinillos Bayona, A., Pye, H., Mosse, C. A., Callan, J., MacRobert, A., ... 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