Polymer directed enzyme prodrug therapy PDEPT

Polymer directed enzyme prodrug therapy (PDEPT) 

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Figure 16 Polymer directed enzyme prodrug therapy (PDEPT). Panel (a) is a schematic showing the two-step approach taken to realize PDEPT panels (b) and (c) show a combination that utilizes HPMA-copolymer-glycine-glycine-cephalosporin-doxorubicin as the macromolecular prodrug and HPMA copolymer jS-lactamase conjugate as the activating enzyme. (From Refs. 141,142.)...

Fig. 14 A Polymer directed enzyme prodrug therapy (PDEPT) is a two-step approach that relies on activation of a polymer-drug conjugate by a complementary polymer-enzyme conjugate B PKl activated HPMA copolymer-Gly-Gly-cathepsin B C HPMA copolymer-Gly-Gly-cephalosporin-doxorubicin activated by HPMA copolymer-Gly-Gly-/3-lactamase D Etoposide prodrug (candidate for polymer conjugation) activated by HPMA copolymer-catalytic antibody 38C2...

Satchi R, Connors TA, Duncan R. PDEPT Polymer directed enzyme prodrug therapy. I. HPMA copolymer-cathepsin B and PKl as a model combination. Brit J Cancer 2001 85 1070-1076. 

As an example of a selectively acting drug carrier, we would like to mention also the PDEPT (polymer-directed enzyme prodrug therapy) approach based on combination of HPMA copolymer prodrug with the poly(HPMA)-enzyme conjugate selectively generating the cytotoxic drug within tumor. As an example a combination of PKl and polymer-cathepsin B system can be cited but also other combinations were tested. HPMA-based polymers with a micellar or dendritic structure have been also intensively studied they are described in separate chapters. 

R. Satchi-Fainaro et al., PDEPT polymer-directed enzyme prodrug therapy. 2. HPMA copolymer-beta-lactamase and HPMA copolymer-C-Dox as a model combination. Bioconjug. Chem., 14(4), 797-804 (2003). 

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