Cell death triggered by photodynamic therapy can occur through different mechanisms: apoptosis, necrosis or autophagy. However, recent studies have demonstrated the existence of other mechanisms with characteristics of both necrosis and apoptosis. These new cell death pathways, collectively termed regulated necrosis, include a variety of processes triggered by different stimuli. In this study, we evaluated the cell death mechanism induced by photodynamic treatments with two photosensitizers, meso-tetrakis (4-carboxyphenyl) porphyrin sodium salt (Na-H₂TCPP) and its zinc derivative Na-ZnTCPP, in two human breast epithelial cell lines, a non-tumoral (MCF-10A) and a tumoral one (SKBR-3). Viability assays showed that photodynamic treatments with both photosensitizers induced a reduction in cell viability in a concentration-dependent manner and no dark toxicity was observed. The cell death mechanisms triggered were evaluated by several assays and cell line-dependent results were found. Most SKBR-3 cells died by either necrosis or apoptosis. By contrast, in MCF-10A cells, necrotic cells and another cell population with characteristics of both necrosis and apoptosis were predominant. In this latter population, cell death was PARP-dependent and translocation of AIF to the nucleus was observed in some cells. These characteristics are related with parthanatos, being the first evidence of this type of regulated necrosis in the field of photodynamic therapy.

The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

Temocene, a porphycene analogue of temoporfin, has been synthesized. Compared to temoporfin, temocene is endowed with 2.5-fold larger absorption coefficients in the red part of the spectrum while keeping its excellent photophysical and singlet oxygen photosensitization ability. While its photodynamic activity towards HeLa cells is lower than that of temoporfin, its higher photostability, lower dark toxicity and mitochondrial localisation make temocene a promising candidate for photodynamic therapy applications.

Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.

Two novel porphyrin-core systems were prepared by Sonogashira cross-coupling of the terminal alkyne groups of meso-tetra(4-ethynylphenyl)porphyrin-Zn(II) (P-1) with halogenated Ru(II)- or Ir(III)-phenanthroline complexes. The resulting compounds (P-Ru and P-Ir) were spectroscopically characterised and their photophysical properties were investigated (λ_em 625, 665 nm; τ_T 339.6 μs (P-Ru) and λ_em 530, 612, 664 nm; τ_T 396.6 μs (P-Ir)). Nanosecond time-resolved transient absorption studies were used to explore the ³MLCT nature of the triplet excited states, and the singlet oxygen quantum yields were determined (Φ_Δ 44.8 (P-Ru), 33.2 (P-Ir)%). The subcellular uptake of P-Ru and P-Ir and their application as photosensitisers (PS) in photodynamic therapy (PDT) were explored due to their solution photophysics and absence of dark toxicity. Upon irradiation (λ_exc = 620–630 nm; 10 min; 33 J cm⁻²), both P-Ru and P-Ir killed 90% of SKBR-3 cells at 1 μM. Notably P-Ru induced a 77% decrease in cell viability at only 0.25 μM.