Inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by liposome-delivered photosensitising agents.
The uptake of two photosensitising agents (hematoporphyrin and chlorophyll a) by a highly pathogenic bacterium, namely methicillin-resistant Staphylococcus aureus (MRSA), has been studied by using unilamellar liposomes of different size, fluidity and electric charge as carriers. Optimal results are obtained by using hematoporphyrin embedded in fluid cationic vesicles composed by the monocationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), which yield an endocellular concentration of photosensitiser much higher than that obtained by incubation of the cells with the free porphyrin, yet promote a tighter binding and a more efficient photoinactivation of MRSA. Apparently, the photosensitiser is successfully transferred from the liposome to the bacterial cells when the presence of the tetrapyrrolic derivative does not appreciably perturb the native three-dimensional organisation of the lipid vesicle, such as it occurs with hematoporphyrin. On the other hand, chlorophyll, which causes a marked structural alteration of the DOTAP vesicles as shown by electron microscopy and fluorescence anisotropy measurements, does not show any detectable photocytotoxicity toward MRSA, contrary to what observed for the free dye.
Ferro
Stefania
S
CNR Institute of Biomedical Technologies, Metalloproteins Unit, Department of Biology, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Ricchelli
Fernanda
F
Mancini
Giovanna
G
Tognon
Giuseppe
G
Jori
Giulio
G
D002734:Chlorophyll / Q000008:administration & dosage; D000077194:Chlorophyll A; D005229:Fatty Acids, Monounsaturated; D006415:Hematoporphyrins / Q000008:administration & dosage; D066298:In Vitro Techniques; D008081:Liposomes; D016106:Methicillin Resistance; D018462:Photobiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D000644:Quaternary Ammonium Compounds; D013053:Spectrophotometry; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
D005229:Fatty Acids, Monounsaturated; D006415:Hematoporphyrins; D008081:Liposomes; D017319:Photosensitizing Agents; D000644:Quaternary Ammonium Compounds; D002734:Chlorophyll; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D000077194:Chlorophyll A