Despite specialists’ efforts to find the best solutions for cancer diagnosis and therapy, this pathology remains the biggest health threat in the world. Global statistics concerning deaths associated with cancer are alarming; therefore, it is necessary to intensify interdisciplinary research in order to identify efficient strategies for cancer diagnosis and therapy, by using new molecules with optimal therapeutic potential and minimal adverse effects. This review focuses on studies of porphyrin macrocycles with regard to their structural and spectral profiles relevant to their applicability in efficient cancer diagnosis and therapy. Furthermore, we present a critical overview of the main commercial formulations, followed by short descriptions of some strategies approached in the development of third-generation photosensitizers.

Cu(II) complexes with asymmetrical and symmetrical porphyrinic ligands were synthesized with superior yields using microwave irradiation. The paper presents the synthesis of 5-(3-hydroxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl)-21,23-Cu(II)-porphine in comparison to its symmetrical complex 5,10,15,20-meso-tetrakis-(4-carboxy-methylphenyl)-21,23-Cu(II) porphine. The two compounds were characterized by FT-IR, UV–Vis and EPR spectroscopy, which fully confirmed the structures. The spectral molecular absorption properties of the porphyrinic complexes were studied in organic solvents (methanol, ethanol, iso-propanol, dimethyl sulfoxide, dimethylformamide and methylene chloride), and the influence of the solvent polarity on the absorbance maxima is described. In order to establish their future potential in biomedical applications preliminary toxicological studies consisting of viability and proliferation of standard tumor cell lines (MCF7 and B16) testing was performed. The obtained results indicate a low toxicity for both compounds and further recommends them for testing in light activation protocols.

This paper deals with a series of new unsymmetrically substituted mesoporphyrins: 5‐(2‐hydroxyphenyl)‐10,15,20‐tris‐phenyl‐21,23‐H‐porphyrin (TPPOH_O), 5‐(3‐hydroxyphenyl)‐10,15,20‐tris‐phenyl‐21,23‐H‐porphyrin (TPPOH_M), 5‐(4‐hydroxyphenyl)‐10,15,20‐tris‐phenyl‐21,23‐H‐porphyrin (TPPOH_P), 5‐(2‐hydroxyphenyl)‐10,15,20‐tris‐butyl‐21,23‐H‐porphyrin (TBPOH_O), and their parent nonsubstituted compounds, respectively, 5,10,15,20‐tetrakis‐phenyl‐21,23‐H‐porphyrin (TPP) and 5,10,15,20‐tetrakis‐butyl‐21,23‐H‐porphyrin (TBP). Several photophysical studies were carried out to access the influence of the unsymmetrical substitution at the porphyrinic macrocycle on porthyrin′s photophysical properties, especially porthyrin′s efficiency as singlet oxygen sensitizers. The quantum yields of singlet oxygen generation were determined in benzene (Φ_Δ(TPP) = 0.66 ± 0.05; Φ_Δ(TPPOH_O) = 0.69 ± 0.04; Φ_Δ(TPPOH_M) = 0.62 ± 0.04; Φ_Δ(TPPOH_P) = 0.73 ± 0.03; Φ_Δ(TBP) = 0.76 ± 0.03; Φ_Δ(TBPOH_O) = 0.73 ± 0.02) using the 5,10,15,20‐tetraphenyl‐21,23‐H‐porphine (Φ_Δ(TPP) = 0.66) and Phenazine (Φ_Δ(Phz) = 0.83) as reference compounds. Their fluorescence quantum yields were found to be (Φ_f(TPPOH_O) = 0.10 ± 0.04; Φ_f(TPPOH_M) = 0.09 ± 0.03; Φ_f(TPPOH_P) = 0.13 ± 0.02; Φ_f(TBP) = 0.08 ± 0.03 and Φ_f(TBPOH_O) = 0.08 ± 0.02 using 5,10,15,20‐tetraphenyl‐21,23‐H‐porphine as reference Φ_f(TPP) = 0.13). Singlet state lifetimes were also determined in the same solvent. All the porphyrins presented very similar fluorescence lifetimes (mean values of τ_S (with O₂, air equilibrated) = 9.6 ± 0.3 nanoseconds and (without O₂, argon purged) = 10.1 ± 0.6 nanoseconds, resp.). The phosphorescence emission was found to be negligible for this series of unsymmetrically substituted mesoporphyrins, but an E‐type, thermally activated, delayed fluorescence process was proved to occur at room temperature.

: We designed three unsymmetrical meso-tetrasubstituted phenyl porphyrins for further development as theranostic agents for cancer photodynamic therapy (PDT): 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P2.2), Zn(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Zn(II)2.2) and Cu(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Cu(II)2.2). The porphyrinic compounds were synthesized and their structures were confirmed by elemental analysis, FT-IR, UV-Vis, EPR and NMR. The compounds had a good solubility in polar/nonpolar media. P2.2 and, to a lesser extent, Zn(II)2.2 were fluorescent, albeit with low fluoresence quantum yields. P2.2 and Zn(II)2.2 exhibited PDT-acceptable values of singlet oxygen generation. A “dark” cytotoxicity study was performed using cells that are relevant for the tumor niche (HT-29 colon carcinoma cells and L929 fibroblasts) and for blood (peripheral mononuclear cells). Cellular uptake of fluorescent compounds, cell viability/proliferation and death were evaluated. P2.2 was highlighted as a promising theranostic agent for PDT in solid tumors considering that P2.2 generated PDT-acceptable singlet oxygen yields, accumulated into tumor cells and less in blood cells, exhibited good fluorescence within cells for imagistic detection, and had no significant cytotoxicity in vitro against tumor and normal cells. Complexing of P2.2 with Zn(II) or Cu(II) altered several of its PDT-relevant properties. These are consistent arguments for further developing P2.2 in animal models of solid tumors for in vivo PDT.

Malignant skin conditions are classified as the most common forms of cancer, with an evolution of one million new cases reported every year. Research efforts in the medical field are focused on developing innovative strategies for the dissemination of measures for preventing cancer and providing new antitumor compounds. The present research examines the development and evaluation of 1% Carbopol-based hydrogels incorporating two porphyrin derivatives—5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2)—to create formulations suitable for topical photodynamic therapy (PDT) applications. The physicochemical properties of the obtained hydrogels were carefully evaluated, revealing the successful integration of the porphyrins into the 1% Carbopol hydrogel matrix. Rheological analysis demonstrated pseudoplastic behavior, with an increase in viscosity properties for P2.1 and P2.2, suggesting interactions with the Carbopol polymer structure. UV-visible and fluorescence spectroscopy confirmed the maintenance of the porphyrins’ photodynamic properties, essential for therapeutic efficacy. Pharmacotechnical studies highlighted the hydrogels’ suitability for topical applications. The formulations maintained an optimal pH range, ensuring skin compatibility and minimizing the potential for skin irritation. Their mechanical properties, including elasticity and rigidity, provided stability during handling and application. The high swelling capacity indicated effective moisture retention, enhancing skin hydration and drug release potential. Furthermore, the hydrogels demonstrated excellent spreadability, enabling uniform application and coverage, crucial for efficient light activation of the photosensitizers. The combination of robust physicochemical and pharmacotechnical properties highlights the potential of these porphyrin-loaded 1% Carbopol hydrogels as promising carriers for topical PDT. These results permit further biological and therapeutic investigations to optimize the formulation for clinical use, advancing the development of effective localized photodynamic therapies.