1. Introduction

N-heterocyclic macrocycles well-known for their mediation in important biological functions, such as respiration and photosynthesis, but also by their role in a wide range of clinical and non-clinical applications that have high impacts on human life ^[1][2][3]. Natural tetrapyrrolic macrocycles like heme (iron(II) complex of PP-IX) and chlorophylls (

Figure 1), but also the synthetic porphyrins and analogs ones (e.g., benzoporphyrins, chlorins, phthalocyanines) ^[4][5] are recognized to present unique structural, physicochemical, and photochemical features to be used in the development of dyes for dye-sensitized solar cells (DSSC) ^{[6][7][8][9][10][11][12][13]}, (chemo) sensors ^{[14][15][16][17][18][19][20]}, (photo)catalysts ^{[21][22][23][24][25][26][27]}, biomarkers ^[14][28][29] or as therapeutic photosensitizers (PS) ^{[30][31][32][33][34][35][36][37][38][39][40]}, among other applications ^[1].

Figure 1.

 General structure of the porphyrinic nucleus and natural derivatives, such as chlorophyll 

a

 and 

b

, and heme.

Figure 2

¹

₂

Figure 2B) are particularly relevant for their success to mediate the photodynamic process in photodynamic therapy (PDT) against tumoral cells ^{[33][36][41][42]}, but also toward non-oncological pathologies, such as age-related macular degeneration. In the last two decades, porphyrinoids (either as free-base or coordinated with different metals) have been recognized as highly efficient PS to eradicate a broad range of microorganisms including drug-resistant strains using the same concept of PDT ^{[31][37][43][44][45][46][47][48][49][50]}.

Figure 2.

 (

A

) Electromagnetic spectrum and typical absorption spectrum of porphyrins (blue line), chlorins (green line) and phthalocyanines (red line). (

B

) Simplified Jablonski diagram and reactive oxygen species (ROS) generation.

2. PDT

Figure 2

¹

³

³

₂

¹

₂⁻

₂

₂

Figure 2B) ^[51][52][53]. Such radicals are then responsible for the elimination of undesirable bacteria.

Recently, the potential of PDT for tissue regeneration has caught the attention of many research groups concerning the role of non-porphyrinoid PS for skin wound healing, as was recently highlighted in our previous review ^[54]. In that review article, it is discussed that the PDT process not only enhances the mitochondrial activity, respiratory chain, and ATP synthesis ^[52][55], but also recruits important metalloproteinases (MMP)/growth factors (GF) and activate signal-regulated kinases ^[56][57] that are critical for the differentiation and proliferation of skin cells (such as fibroblasts) and extracellular matrix (ECM) components (such as elastin and collagen) ^{[53][56][57][58]} (

Figure 3

in situ,

Figure 2

Figure 3.

 Schematic representation of tetrapyrrolic macrocycles photosensitizers (PS) contribution for wound healing.

The PS studies comprised (i) first-generation, consisting of mixtures obtained from natural occurring porphyrins (e.g., hematoporphyrin derivative, Photofrin); (ii) second-generation, such as porphyrins, chlorins, benzoporphyrins and phthalocyanines with pure structures; and (iii) third-generation, resulting from the combination of second-generation PS with specific delivery carriers, such as antibodies, liposomes, polymers, nanoparticles, and micelles to overcome the drawbacks of the other two PS generations, such as low accumulation on the desired site, self-aggregation and low solubility in aqueous media ^[46][59][60].

^®

^®

^®

^®

^®

^®

^®