Like a bolt from the blue: phthalocyanines in biomedical optics

Abstract

The purpose of this review is to compile preclinical and clinical results on phthalocyanines (Pcs) as photosensitizers (PS) for Photodynamic Therapy (PDT) and contrast agents for fluorescence imaging. Indeed, Pcs are excellent candidates in these fields due to their strong absorbance in the NIR region and high chemical and photo-stability. In particular, this is mostly relevant for their in vivo activation in deeper tissular regions. However, most Pcs present two major limitations, i.e., a strong tendency to aggregate and a low water-solubility. In order to overcome these issues, both chemical tuning and pharmaceutical formulation combined with tumor targeting strategies were applied. These aspects will be developed in this review for the most extensively studied Pcs during the last 25 years, i.e., aluminium-, zinc- and silicon-based Pcs.

Figure 1

Chemical structures of clinically relevant “non-phthalocyanine” photosensitizers.

Figure 2

(a) General chemical structure of metallated phthalocyanines; (b) Typical absorption and emission spectra of metallated Pc (e.g., zinc based phthalocyanine in DMSO).

Figure 3

A homologous series of AlPc alkylsulfonamides.

Figure 4

Chemical structure of the bombesin-AlPcS₄ conjugate 5 for the targeting of GRPR.

Figure 5

Chemical structure of AlPc 6–10 [106,107].

Figure 6

Structures of compounds 11, 12 and 13 [122].

Figure 7

Chemical structure of phthalocyanine 14i.e., ZnPcS₂P₂.

Figure 8

Chemical structure of hydroxylated phthalocyanines 15–21.

Figure 9

Structure of the fluorinated ZnPc 22, 23 and 24.

Figure 10

Structure of the zinc hexadecafluorinated Pc 25 and its monosulfonated analogue 26.

Figure 11

Chemical structure of octapentyl and octadecyl ZnPcs 27 and 28.

Figure 12

Chemical structure of phthalocyanines 29 and 30.

Figure 13

Structure of compounds 31–34.

Figure 14

Structure of compounds 35, 36 and 37.

Figure 15

Chemical structure of phthalocyanines 38–43.

Figure 16

Chemical structure of compounds 44–48.

Figure 17

Chemical structure of Pc 4 (49) and derivatives 50–58 [187,188,189,190,191,192,193,194].