Porphyrin Macrocycles: General Properties and Theranostic Potential

Abstract

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.

Keywords: photodynamic therapy; porphyrin macrocycles; theranostic agents.

Figure 2

Absorption spectra for: 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl) porphyrin (P), 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl)porphyrinatozinc(II) (ZnP) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl)porphyrinatocopper(II) (CuP); (dimethylsulfoxide used as solvent) [31].

Figure 1

General structures of (a) free base porphyrin and (b) metalloporphyrin (atoms numbered according to IUPAC (https://doi.org/10.1351/goldbook). (accessed date: 17 January 2023).

Figure 3

Fluorescence emission spectra for 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl) porphyrin (P), 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl)porphyrinatozinc(II) (ZnP) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris(4-carboxymethylphenyl)porphyrinatocopper(II) (CuP) (ethanol used as solvent) [23].

Figure 4

Jablonsky diagram (S₀₋ground state of photosensitizer; S₁, S₂, excited singlet states of photosensitizer; T₁, excited triplet state of photosensitizer).

Figure 5

Representative laser scanning microscopy image of 5-(4-hydroxy-3-methoxyphenyl)-10,15,20–tris(4-acetoxy-3-methoxyphenyl) porphyrin (10 µM) uptake by human HT-29 colon carcinoma cells: (A): porphyrin (red) scattered throughout cytosol compared to control (B); (C): 3D volume rendering of 2.36 μm z-stack from A; nuclei were stained with DAPI (blue); scale bar 10 μm in (A,B) and 20 μm in (C) [160].

Figure 6

Structures of porphyrin type macrocycles functionalized with fragments of diethylaminopentyl alchol (a) [154], ethylenediaminetetraacetic acid (b) [156], isoquinoline (c) [182], glucopyranoside (d) [157].

Figure 6

Structures of porphyrin type macrocycles functionalized with fragments of diethylaminopentyl alchol (a) [154], ethylenediaminetetraacetic acid (b) [156], isoquinoline (c) [182], glucopyranoside (d) [157].

Figure 7

Structures of chlorin type macrocycles functionalized with lysine and aspartate fragments (a) [183] or hydrophobic amide groups (b) [184].

Figure 8

Structures of macrocycles photosensitizers functionalized with maltotriose (a) [185] or galactose (b) [185] fragments.

Figure 9

New covalent bond formed after transesterification reaction of TCMP with silanol groups of the surface of silica-coated magnetite nanoparticles [190].