RESUMO
The combination of photodynamic therapy and chemotherapy is a promising strategy to enhance cancer therapeutic efficacy and reduce drug resistance. In this study two zinc(II) phthalocyanine-tin(IV) conjugates linked by a triethylene glycol chain were synthesized and characterized. In these complexes, the zinc(II) phthalocyanine was used as a potential photosensitizer for PDT and the tin complex was selected as cytostatic moiety. The two dyads composed of zinc(II) phthalocyanine and tin complexes exhibited high cytotoxicity, in absence of light stimulation, against MCF-7 human breast cancer cells with low LC50 values in the range of 0.016-0.453 µM. In addition, these complexes showed superior cytotoxicity than their mixture of equimolar component, accompanied with a higher activity towards cancer cells compared to human healthy fibroblasts. However, under irradiation of the zinc phthalocyanine unit (at 650 nm) no photodynamic activity could be detected, due to the most likely quenching of zinc(II) phthalocyanine singlet excited state by the nearby tin complex according to a photoinduced electron transfer process. This study demonstrates the potential of heterometallic anticancer chemotherapeutics composed of a zinc phthalocyanine and tin complex, and it highlights that the development of such conjugates requires that the sensitizer preserves its photophysical properties and in particular its singlet oxygen sensitization ability in the conjugate in order to combine the PDT activity with the cytotoxicity of the anticancer drug.
RESUMO
Driven by their distinctive physiological activities, biological properties and unique theranostic modalities, silicon nanoparticles (SiNPs) are one of the promising materials for the development of novel multifunctional nanoplatforms for biomedical applications. In this work, we assessed the possibility to use laser-synthesized Si NPs as photosensitizers in two-photon excited photodynamic therapy (TPE-PDT) modality. Herein, we used an easy strategy to synthesize ultraclean and monodispersed SiNPs using laser ablation and fragmentation sequences of silicon wafer in aqueous solution, which prevent any specific purification step. Structural analysis revealed the spherical shape of the nanoparticles with a narrow size distribution centered at the mean size diameter of 62 nm ± 0.42 nm, while the negative surface charge of -40 ± 0.3 mV ensured a great stability without sedimentation over a long period of time. In vitro studies on human cancer cell lines (breast and liver) and healthy cells revealed their low cytotoxicity without any light stimulus and their therapeutic potential under TPE-PDT mode at 900 nm with a promising cell death of 45% in case of MCF-7 breast cancer cells, as a consequence of intracellular reactive oxygen species release. Their luminescence emission inside the cells was clearly observed at UV-Vis region. Compared to Si nanoparticles synthesized via chemical routes, which are often linked to additional modules with photochemical and photobiological properties to boost photodynamic effect, laser-synthesized SiNPs exhibit promising intrinsic therapeutic and imaging properties to develop advanced strategy in nanomedicine field.
