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Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges

Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges

Duncan, Ruth and Richardson, Simon (2012) Endocytosis and intracellular trafficking as gateways for nanomedicine delivery: opportunities and challenges. Molecular Pharmaceutics, 9 (9). pp. 2380-2402. ISSN 1543-8384 (Print), 1543-8392 (Online) (doi:10.1021/mp300293n)

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Abstract

More than 40 nanomedicines are already in routine clinical use with a growing number following in preclinical and clinical development. The therapeutic objectives are often enhanced disease- specific targeting (with simultaneously reduced access to sites of toxicity) and, especially in the case of macromolecular biotech drugs, improving access to intracellular pharmacological target receptors. Successful navigation of the endocytic pathways is usually a prerequisite to achieve these goals. Thus a comprehensive understanding of endocytosis and intracellular trafficking pathways in both the target and bystander normal cell type(s) is essential to enable optimal nanomedicine design. It is becoming evident that endocytic pathways can become disregulated in disease and this, together with the potential changes induced during exposure to the nanocarrier itself, has the potential to significantly impact nanomedicine performance in terms of safety and efficacy. Here we overview the endomembrane trafficking pathways, discuss the methods used to determine and quantitate the intracellular fate of nanomedicines, and review the current status of lysosomotropic and endosomotropic delivery. Based on the lessons learned during more than 3 decades of clinical development, the need to use endocytosis-relevant clinical biomarkers to better select those patients most likely to benefit from nanomedicine therapy is also discussed.

Item Type: Article
Additional Information: [1] First published online: 30 July 2012. [2] Published in print: 4 September 2012.
Uncontrolled Keywords: endocytosis, nanomedicine, endosome, lysosome, trafficking, lysosomotropic delivery, endosomotropic delivery
Subjects: R Medicine > RS Pharmacy and materia medica
Faculty / Department / Research Group: Faculty of Engineering & Science > Department of Life & Sports Sciences
Related URLs:
Last Modified: 17 Oct 2016 09:12
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/10608

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