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Article Dans Une Revue ACS Nano Année : 2011

Squalene based nanocomposites: a new platform for the design of multifunctional pharmaceutical theragnostics.

José L Arias
  • Fonction : Auteur
L Harivardhan Reddy
  • Fonction : Auteur
Mohammad Othman
  • Fonction : Auteur
Didier Desmaële
Fatima Zouhiri
  • Fonction : Auteur
Franco Dosio
  • Fonction : Auteur
Ruxandra Gref
Patrick Couvreur

Résumé

This study reports the design of a novel theragnostic nanomedicine which combines (i) the ability to target a prodrug of gemcitabine to an experimental solid tumor under the influence of a magnetic field with (ii) the imaging of the targeted tumoral nodule. This concept is based on the inclusion of magnetite nanocrystals into nanoparticles (NPs) constructed by self-assembling molecules of the squalenoyl gemcitabine (SQgem) bioconjugate. The nanocomposites are characterized by an unusually high drug loading, a significant magnetic susceptibility, and a low burst release. When injected to the L1210 subcutaneous mice tumor model, these magnetite/SQgem NPs were magnetically guided, and they displayed considerably greater anticancer activity than the other anticancer treatments (magnetite/SQgem NPs nonmagnetically guided, SQgem NPs, or gemcitabine free in solution). The histology and immunohistochemistry investigation of the tumor biopsies clearly evidenced the therapeutic superiority of the magnetically guided nanocomposites, while Prussian blue staining confirmed their accumulation at the tumor periphery. The superior therapeutic activity and enhanced tumor accumulation has been successfully visualized using T(2)-weighted imaging in magnetic resonance imaging (MRI). This concept was further enlarged by (i) the design of squalene-based NPs containing the T(1) Gd(3+) contrast agent instead of magnetite and (ii) the application to other anticancer squalenoyls, such as, cisplatin, doxorubicin, and paclitaxel. Thus, by combining different anticancer medicines as well as contrast imaging agents in NPs, we open the door toward generic conceptual framework for cancer treatment and diagnosis. This new theragnostic nanotechnology platform is expected to have important applications in cancer therapy.

Domaines

Chimie organique
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Dates et versions

hal-00589109 , version 1 (27-04-2011)

Identifiants

Citer

José L Arias, L Harivardhan Reddy, Mohammad Othman, Brigitte Gillet, Didier Desmaële, et al.. Squalene based nanocomposites: a new platform for the design of multifunctional pharmaceutical theragnostics.. ACS Nano, 2011, 5 (2), pp.1513-21. ⟨10.1021/nn1034197⟩. ⟨hal-00589109⟩
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