No abstract

Efficient intratumor delivery of anticancer drugs and photosensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole-mount two-color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 mum diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.

No abstract

The present study evaluates the impact of the fluence rate of red light irradiation (λ = 650 nm) on photodynamic efficacy in mTHPC-sensitized HT29 and Colo26 spheroids. Photocytotoxicity, computed as product of the cell yield and plating efficiency, increased progressively when the fluence rate was reduced from 90 to 30 mW cm-2 in both types of spheroids. The observed photocytotoxicity was mainly due to an immediate rather than a delayed cell death for HT29 spheroids. An opposite effect was observed for Colo26 spheroids. The plausible explanations could be the difference in penetration of mTHPC into the spheroids as well as their heterogeneous structure.

The present study evaluates the impact of the fluence rate of red light irradiation (λ = 650 nm) on photodynamic efficacy in mTHPC-sensitized HT29 and Colo26 spheroids. Photocytotoxicity, computed as product of the cell yield and plating efficiency, increased progressively when the fluence rate was reduced from 90 to 30 mW cm -2 in both types of spheroids. The observed photocytotoxicity was mainly due to an immediate rather than a delayed cell death for HT29 spheroids. An opposite effect was observed for Colo26 spheroids. The plausible explanations could be the difference in penetration of mTHPC into the spheroids as well as their heterogeneous structure.