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Polymers 2014, 6(8), 2186-2220; doi:10.3390/polym6082186

Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK
These authors contributed equally to this work.
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Received: 19 February 2014 / Revised: 28 June 2014 / Accepted: 14 July 2014 / Published: 20 August 2014
(This article belongs to the Special Issue Polymers for Drug Delivery)
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Abstract

Polymer-drug conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-drug conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive accumulation of this technology into the tumour tissue (enhanced permeability and retention (EPR) effect) and (ii) the presence of a specific trigger at the tumour site, for selective drug release (e.g., the enzyme cathepsin B). Here, we retrospectively analyse literature data to investigate which tumour types have proved more responsive to polymer-drug conjugates and to determine correlations between the magnitude of the EPR effect and/or expression of cathepsin B. Lung, breast and ovarian cancers showed the highest response rate (30%, 47% and 41%, respectively for cathepsin-activated conjugates and 31%, 43%, 40%, across all conjugates). An analysis of literature data on cathepsin content in various tumour types showed that these tumour types had high cathepsin content (up to 3835 ng/mg for lung cancer), although marked heterogeneity was observed across different studies. In addition, these tumour types were also reported as having a high EPR effect. Our results suggest that a pre-screening of patient population could bring a more marked clinical benefit. View Full-Text
Keywords: polymer-drug conjugate; enhanced permeability and retention effect; cathepsin; tumour microenvironment polymer-drug conjugate; enhanced permeability and retention effect; cathepsin; tumour microenvironment
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Rajora, A.K.; Ravishankar, D.; Osborn, H.M.I.; Greco, F. Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates. Polymers 2014, 6, 2186-2220.

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