Preclinical and pilot clinical cancer studies using fluorescence-guided photodynamic therapy with chlorin e6-polyvinylpyrrolidone and hypericin

Abstract

Photodynamic therapy (PDT) and fluorescence diagnosis is emerging as promising biophotonic strategies for non-invasive treatment and diagnosis of cancers. PDT involves either local or systemic administration of a photosensitising drug, which preferentially localises within the tumour, followed by illumination of the involved organ with light from a laser source. Here, we provide a selective overview of our experience with fluorescence diagnosis and PDT, specifically with regards to the photosensitisers chlorin e6 - polyvinylpyrrolidone and hypericin. We first review our in vivo studies evaluating the potential of both photosensitisers as photodiagnostic and PDT agents. A summary of important molecular mechanisms of PDT in combination with antiangiogenesis therapy is discussed. Then we briefly describe our early clinical experience in chlorin e6-polyvinylpyrrolidone (Ce6-PVP) mediated PDT and our preliminary studies evaluating the mechanisms behind PDT activated immune response. Preclinical work identified that (a) the extent of tumour necrosis post Ce6-PVP mediated PDT is dependent on the plasma concentration of Ce6-PVP, implying a vascular mediated tumour cell death mechanism, (b) Ce6-PVP localises selectively in the xenografted bladder tumour in contrast to the normal chick chorioallanotic membrane (CAM) tissue, (c) hypoxia inducible factor-1alpha (HIF-1alpha), angiogenic vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression are down-regulated after combination treatment with PDT and antiangiogenic drug. Clinical studies using biopsies from patient treated with Ce6-PVP-PDT suggest that local PDT treatment of tumours lead to induction of an anti-tumour immune response capable of controlling the growth of tumours outside the treatment field, indicating its potential for the treatment of distant metastatic diseases.