Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles.
Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is currently being clinically tested as a photosensitizer for PDT. Unfortunately, Pc4 aggregates in aqueous solutions, which dramatically reduces its PDT efficacy and therefore limits its clinical application. We have encapsulated Pc4 using silica nanoparticles (Pc4SNP), which not only improved the aqueous solubility, stability, and delivery of the photodynamic drug but also increased its photodynamic efficacy compared to free Pc4 molecules. Pc4SNP generated photo-induced singlet oxygen more efficiently than free Pc4 as measured by chemical probe and EPR trapping techniques. Transmission electron microscopy and dynamic light scattering measurements showed that the size of the particles is in the range of 25-30 nm. Cell viability measurements demonstrated that Pc4SNP was more phototoxic to A375 or B16-F10 melanoma cells than free Pc4. Pc4SNP photodamaged melanoma cells primarily through apoptosis. Irradiation of A375 cells in the presence of Pc4SNP resulted in a significant increase in intracellular protein-derived peroxides, suggesting a Type II (singlet oxygen) mechanism for phototoxicity. More Pc4SNP than free Pc4 was localized in the mitochondria and lysosomes. Our results show that these stable, monodispersed silica nanoparticles may be an effective new formulation for Pc4 in its preclinical and clinical studies. We expect that modifying the surface of silicon nanoparticles encapsulating the photosensitizers with antibodies specific to melanoma cells will lead to even better early diagnosis and targeted treatment of melanoma in the future.
Zhao
Baozhong
B
Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Yin
Jun-Jie
JJ
Bilski
Piotr J
PJ
Chignell
Colin F
CF
Roberts
Joan E
JE
He
Yu-Ying
YY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D017646:Organosilicon Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D012822:Silicon Dioxide; D026082:Singlet Oxygen / Q000378:metabolism
D004337:Drug Carriers; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; C082854:silicon phthalocyanine; D026082:Singlet Oxygen; D012822:Silicon Dioxide
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