Self-Assembling Doxorubicin-Tocopherol Succinate Prodrug as a New Drug Delivery System: Synthesis, Characterization, and in Vitro and in Vivo Anticancer Activity.
(2014) Bioconjugate Chemistry — Vol. 25, n° 1, p. 72-81 (2014)
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- Abstract
- Self-assembled prodrugs forming nanoaggregates are a promising approach to enhance the antitumor efficacy and to reduce the toxicity of anticancer drugs. To achieve this goal, doxorubicin was chemically conjugated to d-α-tocopherol succinate through an amide bond to form N-doxorubicin-α-d-tocopherol succinate (N-DOX-TOS). The prodrug self-assembled in water into 250 nm nanostructures when stabilized with d-α-tocopherol poly(ethylene glycol) 2000 succinate. Cryo-TEM analysis revealed the formation of nanoparticles with a highly ordered lamellar inner structure. NMR spectra of the N-DOX-TOS nanoparticles indicated that N-DOX-TOS is located in the core of the nanoparticles while PEG chains and part of the tocopherol are in the corona. High drug loading (34% w/w) and low in vitro drug release were achieved. In vitro biological assessment showed significant anticancer activity and temperature-dependent cellular uptake of N-DOX-TOS nanoparticles. In vivo, these nanoparticles showed a greater antitumor efficacy than free DOX. N-DOX-TOS nanoparticles might have the potential to improve DOX-based chemotherapy.
- Affiliations
Friedrich Schiller University Jena Laboratory of Organic and Macromolecular Chemistry
Citations
Duhem, N., Danhier, F., Pourcelle, V., Schumers, J.-M., Bertrand, O., Le Duff, C. S., Hoeppener, S., Schubert, U. S., Gohy, J.-F., Marchand-Brynaert, J., & Préat, V. (2014). Self-Assembling Doxorubicin-Tocopherol Succinate Prodrug as a New Drug Delivery System: Synthesis, Characterization, and in Vitro and in Vivo Anticancer Activity. Bioconjugate Chemistry, 25(1), 72-81. https://doi.org/10.1021/bc400326y (Original work published 2014)