Factors affecting the selectivity of nanoparticle-based photoinduced damage in free and xenografted chorioallantoic membrane model.

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Date publication

novembre 2013

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BEZDETNAYA-BOLOTINE Lina


Tous les auteurs :
Garrier J, Reshetov V, Grafe S, Guillemin F, Zorin V, Bezdetnaya L

Résumé

Abstract Background: Photodynamic therapy (PDT) is a minimally invasive treatment modality for selective destruction of tumours. Critical anatomical structures, like blood vessels in close proximity to the tumour, could be harmed during PDT. Purpose: This study aims to discriminate the photoinduced response of normal and cancerous tissues to photodamage induced by liposomal formulations of meta-tetra(hydroxyphenyl)chlorin (mTHPC). Methods: Normal vascular and cancerous tissues were represented, respectively, by free and xenografted in vivo model of chick chorioallantoic membrane (CAM). Eggs received an intravenous administration of plain (Foslip(R)) or stabilised formulations (Fospeg(R)). Drug release and liposome destruction were, respectively, determined by photoinduced quenching and nanoparticle tracking analysis. PDT was performed at different drug-light intervals (DLI) with further assessment of photothrombic activity, tumoritropism and photoinduced necrosis. Results: Compared to Foslip(R), Fospeg(R) demonstrated significantly higher stability, slower drug release, better tumoricidal effect and lower damage to the normal vasculature at already 1 h DLI. Discussion: This work suggests that nanoparticle-based PDT selectivity could be optimised by analyzing the photoinduced damage of healthy and tumour tissues. Conclusion: In fine, Fospeg(R) appeared to be the ideal candidate in clinical context due to its potential to destroy tumours and reduce vascular damage to normal tissues at short DLI.

Référence

J Drug Target. 2013 Nov 29.