Porphyrin-Loaded TyroSpheres for the Intracellular Delivery of Drugs and Photoinduced Oxidant Species.
In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere nanoparticles, which are triblock polymer [poly(ethylene glycol)-block-oligo(desaminotyrosyltyrosine octyl ester suberate)-block-poly(ethylene glycol)] aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS2a) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation. The physical and chemical stability of TyroSphere nanoparticles allows them to enter cells and to promote the slow intracellular delivery of part of the PSs. Confocal steady-state and lifetime-resolved fluorescence imaging microscopy data showed that the released PSs are free to target their natural intracellular targets, which are mitochondria and lysosomes for CisDiMPyP and TPPS2a, respectively. The photodynamic efficiency of cell killing was increased considerably compared with the free PSs (∼3×), but the mechanism of cell death was the same as that of the free PSs, which are acute necro-apoptosis for CisDiMPyP and autophagy malfunction for TPPS2a, reflecting the specific damage in mitochondria and lysosomes, respectively. We are confident that TyroSpheres provide a novel and efficient platform to administrate PDT photosensitizers, as well as other drugs with intracellular targets.
['Tsubone|Tayana Mazin|TM|', 'Zhang|Zheng|Z|', 'Goyal|Ritu|R|', 'Santacruz|Carolina|C|', 'Martins|Waleska Kerllen|WK|0000-0003-1502-4606', 'Kohn|Joachim|J|0000-0002-5834-6536', 'Baptista|Mauricio S|MS|0000-0001-7079-7666']
D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D004337:Drug Carriers D006367:HeLa Cells D006801:Humans D008247:Lysosomes D008928:Mitochondria D053758:Nanoparticles D016877:Oxidants D004364:Pharmaceutical Preparations D010778:Photochemotherapy D017319:Photosensitizing Agents D011092:Polyethylene Glycols D011108:Polymers D011166:Porphyrins D026082:Singlet Oxygen
photosensitizer photodynamic therapy drug delivery nanospheres