Application of Porphyrins in Antibacterial Photodynamic Therapy

Abstract

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.

Keywords: antibacterial photodynamic therapy; bacteria; light; nanoparticles; porphyrins.

Figure 1

Schematic illustration of photodynamic reaction on bacterial cell [30].

Figure 2

(A) Tetraphenylporphyrin and (B) 5,10,15-Tris(p-chlorophenyl)-20-(2-hydroxy-3-methoxyphenyl)-21H,23H-porphyrin.

Figure 3

Absorption spectrum of meso-5,10,15,20-tetrakis(3,5-dimethoxyphenyl)porphyrin in dichloromethane.

Figure 4

Porphyrins found in nature [43].

Figure 5

Structures of porphyrin derivatives. (A) Hematoporphrin (HpD); (B) Chlorin; (C) Bacteriochlorin; (D) Phthalocyanine [47].

Scheme 1

Synthesis of tetraphenylporphyrin via Rothemund method.

Scheme 2

Synthesis of Tetraphenylporphyrin via Adler–Longo’s Method.

Scheme 3

Synthesis of meso-tetraphenylporphyrin via Lindsey’s Method.

Scheme 4

Synthesis of meso-substituted porphyrins under microwave irradiation.

Scheme 5

Meso-substituted porphyrin obtained using water as solvent/oxidant microwave irradiation.

Scheme 6

Synthesis of meso-substituted porphyrins using solid acid catalysts.

Scheme 7

Synthesis of meso-substituted porphyrins using solventless reaction conditions.

Scheme 8

Synthesis of meso-substituted porphyrins involving the use of ionic liquids.

Figure 6

Schematic representation of cell wall and cytoplasmic membrane structure in Gram-(−) (left) and Gram-(+) (right) bacteria [12].

Figure 7

Examples of light sources [92].

Figure 8

Structures of TMPyP and ZnTPPS₄.

Figure 9

Structures of neutral porphyrins.

Figure 10

Schematic diagram showing the stages involved in carrying out antimicrobial PDT on a burn infection in mice. (A) Inoculation of the mouse with bacterial suspension; (B) injection with photosensitizer solution; (C) irradiation of the infected site with red light [11,77].

Figure 11

Acne treatment with blue light and endogenous, 5-aminolevulinic acid (ALA)-induced porphyrin. Before treatment (A); after six months of therapy (B) [89].

Figure 12

(A) Clinical situation of a patient before antibacterial photodynamic therapy (aPDT). (B) Injection of the photosensitizer. (C) Irradiation with the diode laser. (D) The clinical situation six months after therapy [137].

Figure 13

Structures of some cationic porphyrin derivatives. (A) Tetra-Py⁺Me; (B) Tri-Py⁺-Me-CO₂H; (C) Tri-Py⁺-Me-CO₂CH₃; (D) Tri-Py⁺-Me-PF₄; (E) Di-Py⁺-Me-Di-CO₂H adj; (F) Di-Py⁺-Me-Di-CO₂H opp; (G) Mono-Py⁺-Me-Tri-CO₂H; [142].