TY - JOUR
T1 - Core–shell poly-methyl methacrylate nanoparticles covalently functionalized with a non-symmetric porphyrin for anticancer photodynamic therapy
AU - Ballestri, Marco
AU - Caruso, Enrico
AU - Guerrini, Andrea
AU - Ferroni, Claudia
AU - Banfi, Stefano
AU - Gariboldi, Marzia
AU - Monti, Elena
AU - Sotgiu, Giovanna
AU - Varchi, Greta
N1 - Funding Information:
This work was supported by the Investigator Grant of the Italian Association for Cancer Research (AIRC) 16740 to G.V.
Publisher Copyright:
© 2018
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/9
Y1 - 2018/9
N2 - Photodynamic therapy (PDT) is an anticancer modality that exploits singlet oxygen and other reactive oxygen species, that are formed by selective irradiation of photosensitive molecules, to kill cancer cells. Most photosensitizers (PS) are hydrophobic and poorly soluble in water and several nanoplatforms have been established to achieve a more efficient delivery. Moreover, the covalent binding of the PS to nanoparticles could in principle reduce unwanted bleaching of the PS, while preserving its photodynamic activity. In this study we report the synthesis of a novel non-symmetrical diaryl-porphyrin suitably modified with a polymerizable pendant, that was used for the preparation of core-shell poly-methyl methacrylate nanoparticles covalently loaded with the diaryl-porphyrin (PMMA@PorVa). Particles, which were prepared with two different porphyrin loadings, are spherical in shape and with a narrow hydrodynamic diameter around 70 nm and a positive zeta potential. Their photo-toxicity was tested against the human colon carcinoma cell line HCT116 and the human ovarian adenocarcinoma cell line SKOV3. PMMA@PorVa were able to inhibit tumor cells proliferation similarly to the free porphyrin, thus confirming that the covalent attachment of the PS to PMMA nanoparticles allows to preserve PS photodynamic activity and in vitro efficacy. Flow cytometric analysis of apoptotic cells demonstrates that, especially in SKOV3 cells, the free diaryl-porphyrin is more effective in inducing apoptosis.
AB - Photodynamic therapy (PDT) is an anticancer modality that exploits singlet oxygen and other reactive oxygen species, that are formed by selective irradiation of photosensitive molecules, to kill cancer cells. Most photosensitizers (PS) are hydrophobic and poorly soluble in water and several nanoplatforms have been established to achieve a more efficient delivery. Moreover, the covalent binding of the PS to nanoparticles could in principle reduce unwanted bleaching of the PS, while preserving its photodynamic activity. In this study we report the synthesis of a novel non-symmetrical diaryl-porphyrin suitably modified with a polymerizable pendant, that was used for the preparation of core-shell poly-methyl methacrylate nanoparticles covalently loaded with the diaryl-porphyrin (PMMA@PorVa). Particles, which were prepared with two different porphyrin loadings, are spherical in shape and with a narrow hydrodynamic diameter around 70 nm and a positive zeta potential. Their photo-toxicity was tested against the human colon carcinoma cell line HCT116 and the human ovarian adenocarcinoma cell line SKOV3. PMMA@PorVa were able to inhibit tumor cells proliferation similarly to the free porphyrin, thus confirming that the covalent attachment of the PS to PMMA nanoparticles allows to preserve PS photodynamic activity and in vitro efficacy. Flow cytometric analysis of apoptotic cells demonstrates that, especially in SKOV3 cells, the free diaryl-porphyrin is more effective in inducing apoptosis.
KW - Cancer
KW - Covalent loading
KW - PMMA nanoparticles
KW - Photodynamic therapy
KW - Porphyrins
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U2 - 10.1016/j.jphotobiol.2018.07.013
DO - 10.1016/j.jphotobiol.2018.07.013
M3 - Article
C2 - 30064063
AN - SCOPUS:85050634915
VL - 186
SP - 169
EP - 177
JO - Journal of Photochemistry and Photobiology B: Biology
JF - Journal of Photochemistry and Photobiology B: Biology
SN - 1011-1344
ER -