A comparative study of the cellular uptake, localization and phototoxicityof meta-tetra(hydroxyphenyl) chlorin encapsulated in surface-modified submicronic oil/water carriers in HT29 tumor cells

The poor selectivity of photosensitizers for tumor tissue remains a drawbac k in photodynamic therapy (PDT) and could be improved by adapted formulatio ns. The cellular uptake, localization and phototoxicity of meta-tetra(hydro xyphenyl) chlorin (mTHPC) encapsulated in submicronic colloidal carriers ha ve been studied in macrophage-like J774 cells and EFT 29 human adenocarcino ma cells. Nanocapsules with an external layer made of poly(D.L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have bee n examined. The cellular uptake by J774, as determined by microspectroflori metry, is reduced with mTHPC encapsulated into surface-modified NCs - PLA-P EG and polox PLA - compared with naked PLA, indicating a possible Limitatio n of the clearance of such carriers by the reticuloendothelial system. Enca psulation also modifies the interaction between mTHPC and HT29 cells. Compa red with the manufacturer's solution (PEG, ethanol, water), the cellular up take is strongly reduced. However, the HT29 phototoxicity is much less affe cted and a protecting effect against plasma proteins is observed. Fluoresce nce microscopy reveals a specific punctate fluorescence pattern with PLA-PE G and polox PLA NCs in contrast to a more diffuse distribution with NE and solution, indicating that photodamage targeting could be different. These f indings suggest that photosensitizers encapsulated into surface-modified na nocapsules could be a promising approach for improving PDT efficacy and thi s has to be confirmed in vivo. (C) 2000 Elsevier Science S.A. All rights re served.