In vitro photodynamic activity of chloro(5,10,15,20-tetraphenylporphyrinato)indium(III) loaded-poly(lactide-co-glycolide) nanoparticles in LNCaP prostate tumour cells.
In(III)-meso-tetraphenylporphyrin (InTPP) was encapsulated into nanoparticles (smaller than 200 nm) of poly(d,l-lactide-co-glycolide) (PLGA) using the emulsification-evaporation technique. The photodynamic efficacy of InTPP-loaded nanoparticles and its cellular uptake was investigated with LNCaP prostate tumour cells, in comparison with the free InTPP. The effects of incubation time (1-3h), drug concentration (1.8-7.7 micromol/L) and incident light dose (15-45 J/cm(2)) with both encapsulated and free InTPP were studied. The type of cell death induced by the photochemical process using both encapsulated and free InTPP was also investigated. Cell viability was reduced more significantly with increasing values of these effects for InTPP-loaded nanoparticles than with the free drug. The cellular death induced by both encapsulated and free InTPP was preponderantly apoptotic. Confocal laser scanning microscopy data showed that the InTPP-loaded nanoparticles, as well free InTPP, were localized in the cells, and always in the perinuclear region. Encapsulated InTPP was measured by the intensity of fluorescence intensity of cell extracts and was three times more internalized into the cells than was the free InTPP. Electron paramagnetic resonance experiments corroborated the participation of singlet oxygen in the photocytotoxic effect of nanoparticles loaded with InTPP.
da Silva
André Romero
AR
Department of Physical Chemistry, Institute of Chemistry, University of Campinas, Caixa Postal 6154, 13084-862 Campinas-SP, Brazil.
Inada
Natalia Mayumi
NM
Rettori
Daniel
D
Baratti
Mariana Ozello
MO
Vercesi
Anibal Eugenio
AE
Jorge
Renato Atilio
RA
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D008027:Light; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D038761:Photobleaching; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011098:Polyglactin 910 / Q000737:chemistry* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D026082:Singlet Oxygen / Q000378:metabolism; D013499:Surface Properties
D004337:Drug Carriers; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D011098:Polyglactin 910; C037832:indium tetraphenylporphyrin; D004121:Dimethyl Sulfoxide