Encapsulation of p-THPP into nanoparticles: cellular uptake, subcellular localization and effect of serum on photodynamic activity.

Abstract

The cellular uptake, localization and efflux of meso-tetra-(4-hydroxyphenyl)porphyrin (p-THPP)-loaded nanoparticles have been studied in EMT-6 tumor cells. The effect of blood serum on photocytotoxicity has also been evaluated. Sub-130 nm nanoparticles based on poly(D,L-lactide-co-glycolide) (PLGA) (50:50 PLGA and 75:25 PLGA) and poly(D,L-lactide) (PLA) have been examined in comparison with free p-THPP. For all formulations tested, uptake of photosensitizer into cells was dependent on concentration, time and temperature. All nanoparticulate formulations accumulated within the cells to a greater extent relative to free drug. Indeed, the fluorescence intensities measured on EMT-6 cells treated with p-THPP-loaded nanoparticulate formulations were at least two-fold higher than those obtained with free dye. Furthermore, the highest accumulation level was found with PLGA nanoparticles. Fluorescence microscopy revealed that endocytosis is a major intracellular sequestration mechanism of these p-THPP formulations and that these were localized into early and late endosomes. The efflux study performed on both nonirradiated and irradiated cells indicated that free and p-THPP-loaded nanoparticles gradually escaped from EMT-6 cells as a function of time. This was more pronounced when cells were treated with nanoparticles and irradiated, reflecting important photodamage. It was also found that regardless of the nanoparticulate formulations tested, p-THPP photocytotoxicity was influenced by the concentration of the serum.

• Authors: Y N Konan, J Chevallier, R Gurny, E Allémann
• Journal: Photochemistry and photobiology (Photochem Photobiol) Vol. 77 Issue 6 Pg. 638-44 (Jun 2003) ISSN: 0031-8655 [Print] United States
• PMID: 12870850 (Publication Type: Journal Article)

Chemical References

• Polyesters
• Polymers
• Porphyrins
• meso-tetra-(4-hydroxyphenyl)porphyrin
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• poly(lactide)

Topics

• Animals
• Biological Transport
• Dose-Response Relationship, Drug
• Fluorescence
• Lactic Acid (chemistry)
• Mammary Neoplasms, Animal (drug therapy, metabolism)
• Mice
• Nanotechnology
• Photochemistry
• Polyesters (chemistry)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polymers (chemistry)
• Porphyrins (metabolism, therapeutic use, toxicity)
• Serum (metabolism)
• Temperature
• Tumor Cells, Cultured