Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model.
OBJECTIVE
Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs.


METHODS
Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 μg/mL) and then to SWs (0.43 mJ/mm(2) for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control.


RESULTS
There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth.


CONCLUSIONS
The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment's efficacy in an in vitro neuroblastoma model.
Department of Drug Science and Technology, University of Torino, Torino, Italy.
Roberto
R
Canaparo
Greta
G
Varchi
Marco
M
Ballestri
Federica
F
Foglietta
Giovanna
G
Sotgiu
Andrea
A
Guerrini
Andrea
A
Francovich
Pierluigi
P
Civera
Roberto
R
Frairia
Loredana
L
Serpe
D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010778:Photochemotherapy; D011108:Polymers; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000528:radiation effects
D011108:Polymers; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C092400:meso-tetrakis(4-sulfonatophenyl)porphyrin
cancer; poly-methyl methacrylate nanoparticles; shockwaves; sonodynamic therapy; ultrasound