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Article Dans Une Revue Theranostics Année : 2012

Multifunctional peptide-conjugated hybrid silica nanoparticles for photodynamic therapy and MRI

Résumé

Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

Dates et versions

hal-00723908 , version 1 (15-08-2012)

Identifiants

Citer

Hamanou Benachour, Aymeric Sève, Thierry Bastogne, Céline Frochot, Régis Vanderesse, et al.. Multifunctional peptide-conjugated hybrid silica nanoparticles for photodynamic therapy and MRI. Theranostics, 2012, 2 (9), pp.889-904. ⟨10.7150/thno.4754⟩. ⟨hal-00723908⟩
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