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

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 chorioallantoïc membrane (CAM). Eggs received an intravenous administration of plain (Foslip®) or stabilised formulations (Fospeg®). 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®, Fospeg® 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® 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.

• CAM
• drug delivery
• liposome
• mTHPC
• nanophotosensitizers
• photodynamic therapy