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

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. Green open access

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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.

Type: Article
Title: Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1088/1361-6528/28/5/055101
Publisher version: http://dx.doi.org/10.1088/1361-6528/28/5/055101
Language: English
Additional information: Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
Keywords: Indocyanine green, polyglutamate, cathepsin B, near infra-red, laser cancer treatment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
URI: https://discovery.ucl.ac.uk/id/eprint/1530852
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