A Novel Approach to a Bifunctional Photosensitizer for Tumor Imaging and Phototherapy

Abstract

Optical imaging has attracted a great attention for studying molecular recognitions because minute fluorescent tracers can be detected in homogeneous and heterogeneous media with existing laboratory instruments. In our preliminary study, a clinically relevant photosensitizer (HPPH, a chlorophyll-a analog) was linked with a cyanine dye (with required photophysical characteristics but limited tumor selectivity), and the resulting conjugate was found to be an efficient tumor imaging (fluorescence imaging) and photosensitizing agent. Compared to HPPH, the presence of the cyanine dye moiety in the conjugate produced a significantly higher uptake in tumor than skin. At a therapeutic/imaging dose, the conjugate did not show any significant skin phototoxicity, a major drawback associated with most of the porphyrin-based photosensitizers. These results suggest that tumor-avid porphyrin-based compounds can be used as "vehicles" to deliver the desired fluorescent agent(s) to tumor. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (fluorescence imaging and photodynamic therapy) provides the potential for tumor detection and targeted photodynamic therapy, combining two modalities into a single cost-effective "see and treat" approach.

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

“…First, the ultra-small size of PLP (<30 nm) might provide an advantage for efficient penetration through the permeable tumor vasculature into the tumor interstitial space, resulting the local enrichment of porphyrins within the tumor (39). Second, porphyrin molecules have their own tumor affinity that could further drive their selective tumor uptake as reported previously (40).…”

Trends in Interdisciplinary Studies Revealing Porphyrinic Compounds Multivalency Towards Biomedical Application

“…We believe that nowadays the analysis of porphyrins and porphyrin-like structures from the point of view of their fluorescence properties is crucial for developing minimally invasive fluorescent tools for diagnosis. Several studies on fluorescent photosensitizers show them as markers and beacons and point toward their dual utility for "seeing and treating" (Chen et al, 2005;Cló et al, 2007). Theranostic nanomedicine, integrating nano-platforms which can diagnose, deliver targeted therapy and monitor response to therapy, is best illustrated in PDT.…”

The role of photodynamic therapy (PDT) physics

“…102 For instance, a photosensitizer may be linked to a fluorescent molecule to enhance its delectability under fluorescence imaging. 103 Pandey et al 104 have proposed combining photosensitizers with contrast agents for optical, MRI and PET imaging, allowing image-guided PDT treatment. Zheng et al have combined the "molecular beacon" concept with a photosensitizer to produce photodynamic molecular beacons.…”