No abstract

No abstract

Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are being considered as nanodelivery systems for photodynamic therapy. The physico-chemical and biological aspects of their use remain largely unknown. Herein we report the results of a study of PLGA NPs for the delivery of the model hydrophobic photosensitizer ZnTPP to HeLa cells. ZnTPP was encapsulated in PLGA with high efficiency and the NPs showed negative zeta potentials and diameters close to 110 nm. Poly(ethylene glycol) (PEG) coating, introduced to prevent opsonization and clearance by macrophages, decreased the size and zeta potential of the NPs by roughly a factor of two and improved their stability in the presence of serum proteins. Photophysical studies revealed two and three populations of ZnTPP and singlet oxygen in uncoated and PEGylated NPs, respectively. Singlet oxygen is confined within the NPs in bare PLGA while it is more easily released into the external medium after PEG coating, which contributes to a higher photocytotoxicity towards HeLa cells in vitro. PLGA NPs are internalized by endocytosis, deliver their cargo to lysosomes and induce cell death by apoptosis upon exposure to light. In conclusion, PLGA NPs coated with PEG show high potential as delivery systems for photodynamic applications.

With the aim of assessing the role of the chemical structure of the photosensitizer on the photophysical and photochemical properties of the final nanoparticle suspension, we have investigated a series of poly-(ethylene glycol)-poly-([Formula: see text]-lactide-co-glycolide) nanoparticles containing a hydrophobic or a hydrophilic porphyrin covalently conjugated to the nanoparticle. Covalent conjugation responded to the objective of trying to improve photosensitizer loading in these nanoparticles, especially for hydrophilic photosensitizers, but also enabled the porphyrins to remain attached to the nanoparticle without necessarily being inside the poly-([Formula: see text]-lactide-co-glycolide) core. This strategy has provided valuable information about the dependence of the photophysical and singlet oxygen photosensitizing properties of the suspensions on the nature of the photosensitizer. It is concluded that poly-([Formula: see text]-lactide-co-glycolide) nanoparticles with covalently-bound hydrophilic porphyrins show superior singlet oxygen photosensitizing ability.