Two-step polymer- and liposome- enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives

Scomparin, Anna, Florindo, Helena F., Tiram, Galia, Ferguson, Elaine L. ORCID: https://orcid.org/0000-0002-0125-0234 and Satchi-Fainaro, Ronit 2017. Two-step polymer- and liposome- enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives. Advanced Drug Delivery Reviews 118 , pp. 52-64. 10.1016/j.addr.2017.09.011

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Abstract

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention – EPR – effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Publisher:	Elsevier
ISSN:	0169-409X
Date of First Compliant Deposit:	23 November 2017
Date of Acceptance:	7 September 2017
Last Modified:	01 Dec 2024 10:30
URI:	https://orca.cardiff.ac.uk/id/eprint/104681

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