title: Poly(D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic therapy: enhancing singlet oxygen release and photototoxicity by surface PEG coating.
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.
authors: Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
authors: Ester
authors: E
authors: Boix-Garriga
authors: Pilar
authors: P
authors: Acedo
authors: Ana
authors: A
authors: Casadó
authors: Angeles
authors: A
authors: Villanueva
authors: Juan Carlos
authors: JC
authors: Stockert
authors: Magdalena
authors: M
authors: Cañete
authors: Margarita
authors: M
authors: Mora
authors: Maria Lluïsa
authors: ML
authors: Sagristá
authors: Santi
authors: S
authors: Nonell
mesh_terms: D017209:Apoptosis; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D026082:Singlet Oxygen / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols