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Issue 5, 2014
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PEG-pHPMAm-based polymeric micelles loaded with doxorubicin-prodrugs in combination antitumor therapy with oncolytic vaccinia viruses

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Abstract

An enzymatically activatable prodrug of doxorubicin was covalently coupled, using click-chemistry, to the hydrophobic core of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl)-methacrylamide-lactate] micelles. The release and cytotoxic activity of the prodrug was evaluated in vitro in A549 non-small-cell lung cancer cells after adding β-glucuronidase, an enzyme which is present intracellularly in lysosomes and extracellularly in necrotic areas of tumor lesions. The prodrug-containing micelles alone and in combination with standard and β-glucuronidase-producing oncolytic vaccinia viruses were also evaluated in vivo, in mice bearing A549 xenograft tumors. When combined with the oncolytic viruses, the micelles completely blocked tumor growth. Moreover, a significantly better antitumor efficacy as compared to virus treatment alone was observed when β-glucuronidase virus treated tumor-bearing mice received the prodrug-containing micelles. These findings show that combining tumor-targeted drug delivery systems with oncolytic vaccinia viruses holds potential for improving anticancer therapy.

Graphical abstract: PEG-pHPMAm-based polymeric micelles loaded with doxorubicin-prodrugs in combination antitumor therapy with oncolytic vaccinia viruses

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Publication details

The article was received on 14 Aug 2013, accepted on 01 Oct 2013 and first published on 03 Oct 2013


Article type: Paper
DOI: 10.1039/C3PY01097J
Citation: Polym. Chem., 2014,5, 1674-1681
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    PEG-pHPMAm-based polymeric micelles loaded with doxorubicin-prodrugs in combination antitumor therapy with oncolytic vaccinia viruses

    E. Ruiz-Hernández, M. Hess, G. J. Melen, B. Theek, M. Talelli, Y. Shi, B. Ozbakir, E. A. Teunissen, M. Ramírez, D. Moeckel, F. Kiessling, G. Storm, H. W. Scheeren, W. E. Hennink, A. A. Szalay, J. Stritzker and T. Lammers, Polym. Chem., 2014, 5, 1674
    DOI: 10.1039/C3PY01097J

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