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.

Stimuli‐responsive liposomes for drug delivery

“…A second generation PS, m ‐THPC (meta‐tetra[hydroxyphenyl]chlorin), has also been used in a PEGylated liposome formulation . Aggregation of m ‐THPC with the lipid shell of the liposomes was observed and triggered the release of m ‐THPC in the form of the monomeric photoactive state once the liposome was degraded.…”

Animal models for photodynamic therapy (PDT)

“…PS can also be topically applied to the xenografted tumours on the CAM. The advantages of this model include the ease of in vivo microscopy to study PDT-induced vascular damage and the lack of regulatory controls on experiments involving eggs [ 7 – 11 ].…”

Tumor grafted – chick chorioallantoic membrane as an alternative model for biological cancer research and conventional/nanomaterial-based theranostics evaluation

“…It was observed that at a DLI of 1 h, tumor accumulation and PDT-induced antitumor effects in terms of necrosis area were better with Fospeg ® than Foslip ® . Additionally, Fospeg ® was found to be less destructive on normal vasculatures [161].…”

“…Bright field microscopy is also extensively used for histological analyses of the harvested tumor and tissues from the embryo. Reagents such as hematoxylin and eosin (H&E; Figure 4(b)), or trichrome stains are applied to distinguish the cellular organelles and stromal components, and to evaluate the conditions of the tumor and TME after treatment [50,156,161].…”

“…Fluorophores like rhodamine derivatives have also been used for angiographies, when examining vascular injury following PDT (Figure 4(c)) [151,171]. Furthermore, PDT-induced vascular occlusion can be visualized and then assessed using scoring systems corresponding to the extent of vascular re-growth and branching after triggering the action of the photosensitizer through light irradiation [161,171]. Attaching fluorophores to human or avian-specific endothelial markers may give information on blood vessel origin.…”