Core–shell poly-methyl methacrylate nanoparticles covalently functionalized with a non-symmetric porphyrin for anticancer photodynamic therapy

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2018-09, Vol.186, p.169-177
• Main Authors: Ballestri, Marco, Caruso, Enrico, Guerrini, Andrea, Ferroni, Claudia, Banfi, Stefano, Gariboldi, Marzia, Monti, Elena, Sotgiu, Giovanna, Varchi, Greta
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; Bleaching; Cancer; Cancer therapies; Cell proliferation; Chemical synthesis; Colon; Covalence; Covalent loading; Flow cytometry; Hydrophobicity; Irradiation; Nanoparticles; Organic chemicals; Photodynamic therapy; Photosensitivity; PMMA nanoparticles; Polymethyl methacrylate; Polymethylmethacrylate; Porphyrins; Radiation; Reactive oxygen species; Singlet oxygen; Toxicity; Toxicity testing; Tumor cells; Zeta potential
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2018.07.013

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. [Display omitted] •Core-shell PMMA nanoparticles covalently loaded with a non-symmetric di-aryl porphyrin were synthesized and characterized.•Porphyrin-loaded PMMA nanoparticles displayed IC50 values in the nanomolar range on HTC116 and SKOV3 cell lines.•Porphyrin-loaded PMMA nanoparticles produce ROS and singlet oxygen upon light irradiation.•Porphyrin-loaded PMMA nanoparticles could represent a valuable system for in vivo PDT applications.