Table 3.

Summary of the main structural modifications made to phthalocyanines (Pcs) in recent years, main aspects and conclusions that can be drawn from their photobiological effects.

Structural Variation	Specification	Main Aspects and Conclusions	References
Metal coordination	Zn, In and GaPcs	Various metals were introduced into benzimidazole tetrasubstituted Pcs. The In-complexed one showed highly efficient singlet oxygen generation and in vitro phototoxicity.	[218]
	RuPcs	Ruthenium complexation can create effective Pcs for PDT, known for its medicinal properties. In addition, loading NO+ and NO2− units onto metal allows the release of nitric oxide, boosting light toxicity and causing selective effects seen in vitro.	[219,220]
Presence of chalcogen atoms	O, S, Se	Bathochromic shifts were observed for S and Se-bearing Pcs. The Se proved beneficial in increasing absorptivity and singlet oxygen production. PDT effects were observed for both derivatives, but the first derivative showed greater efficiency in vitro.	[221]
Charges number	0, 4 or 8 positive charges	Improved properties (singlet oxygen production, water solubility, and cellular uptake) were perceived for cationic compounds compared to neutral ones, and lower half-maximal inhibitory values were observed for eight times positively charged compounds for MCF-7 cells.	[222]
Functionalization with biomolecules	Sugar units	Ruthenium-complexed Pcs were functionalized with glucose, galactose, and mannose. Adding sugar did not enhance cellular uptake, but one-bearing mannose proved better for PDT use.	[223]
		Lactose Si-complexed Pcs proved to be biocompatible, stable in aqueous media, and efficient in ROS generation, showing in vitro high photocytotoxicity and selective tumor accumulation in vivo.	[224]
	Biotin	Biotin-PEG-bearing SiPc has been shown to selectively accumulate in tumor tissue and reduce biotin receptor-overexpressed tumor growth progression in vivo. In addition, PEG units made the potential PS more soluble in water and less prone to aggregation.	[225]
		It was perceived that self-assembled biotin-amine SiPc of different sizes (10, 20, 40, and 90 nm), depending on the percentage of surfactant, exhibited targeting and improved photoactivity in vivo, especially for the 20 nm particles after avidin-presence disassembly.	[226]
	Glycyrrhetinic acid	The interest in conjugating glycyrrhetinic acid to SiPc is due to its overexpressed receptors in liver cancer. The PS candidate was shown to effectively destroy the liver tumor tissue via necrosis and apoptosis. Side effects have not been observed in vivo.	[227]
	Chalcones	Chalcone-bearing cationic Zn- and In-complexed Pcs saw, for MCF-7 breast adenocarcinoma cells, half-maximal inhibitory concentration values reduced to less than half after irradiation. Despite its promise, mechanisms of action still need to be studied.	[228]