Novel photosensitizer-protein nanoparticles for photodynamic therapy: photophysical characterization and in vitro investigations.
In this work two types of pheophorbide-HSA (Pheo-HSA) nanoparticles, PHSA40 and PHSA100, were prepared and their photophysical and photosensitizing properties were investigated. Due to intramolecular interactions the singlet oxygen quantum yield of PHSA40 and PHSA100 is very low (less than 0.1). Intracellular uptake and phototoxicity of pheophorbide a as well as of the Pheo-HSA nanoparticles were studied in Jurkat cells. The HSA nanoparticles do not influence the amount of dye accumulation in cells. After 24h incubation, PHSA40 and PHSA100 showed a higher phototoxicity than Pheo. The reason for this behavior is an efficient nanoparticle decomposition in the cellular lysosomes. The process of drug release during incubation of cells with Pheo-HSA nanoparticles was illustrated by fluorescence lifetime imaging (FLIM) and confocal laser scanning microscopy (CLSM). The final phototoxicity of Pheo-HSA is at the same scale as induced by free Pheo. The drug release ability of HSA nanoparticles shows the possibility to use such formulations as drug carriers in PDT treatment. Therefore, this work constructs a standard for further investigation and optimization of photosensitizer-HSA drug carrier system.
Chen
Kuan
K
Institute of Physics, Humboldt Universität zu Berlin, Newtonstrasse 15, 12489 Berlin, Germany.
Preuss
Annegret
A
Hackbarth
Steffen
S
Wacker
Matthias
M
Langer
Klaus
K
Röder
Beate
B
D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D019169:Jurkat Cells; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D012709:Serum Albumin / Q000737:chemistry* / Q000494:pharmacology; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D017319:Photosensitizing Agents; D012709:Serum Albumin; D002734:Chlorophyll; D026082:Singlet Oxygen; D053148:Caspase 3; C032623:pheophorbide a