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Development of a Novel Triblock Copolymer Therapeutic Nanoreactor

A. Ranquin, C. De Vocht, W. Meier, J. Steyaert and P. Van Gelder
VUB, BE

Keywords:
tribloc copolymers, nanoreactors, enzyme-prodrug therapy

Abstract:
Currently chemotherapy is one of the major strategies to treat cancer patients. It is however limited by several drawbacks such as low bioavailability of chemotoxins, low drug concentrations at the tumor site, systemic toxicity, lack of specificity and drug-resistant tumors. Many different strategies have been proposed to overcome these problems including targeted enzyme-prodrug therapies. However classic enzyme-prodrug therapies suffer from several problems such as immunogenicity of the exogenous enzymes used, non efficient targeting and activation of the prodrugs by endogenous enzymes.
We propose a novel enzyme-prodrug strategy based on the use of therapeutic nanoreactors. In this strategy nanometersized triblock copolymeric (PMOXA-PDMS-PMOXA) vesicles are used to encapsulate the prodrug activating enzyme nucleoside hydrolase of T.vivax. To ensure diffusion of prodrugs and drugs to and from the reactor interior, the nanoreactors are permeabilised by incorporating bacterial outer membrane proteins (OmpF and Tsx) in the reactor wall. We Produced such 200 nm sized nanoreactors and demonstrated the efficient activation of the prodrug 2-fluoroadenosine. We believe that these nanoreactors are promising candidates for in vivo prodrug activation. Targeting of nanoreactors to tumor tissue is possible by the enhanced permeability and retention effect (EPR) and covalent coupling of tumor specific single chain antibodies.

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