Mar 2015 Proceedings of the National Academy of Sciences of the United States of America

Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance.

Auteurs

Wei T, Chen C, Liu J, Liu C, Posocco P, Liu X, Cheng Q, Huo S, Liang Z, Fermeglia M, Pricl S, Liang XJ, Rocchi P, Peng L

Résumé

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.

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