Table 4.

Strategies recently reported on how to structurally improve or enhance certain aspects of boron-dipyrromethene (BODIPY)-based photosensitizers (PSs).

Aim	How?	Main Aspects and Conclusions	References
Long-wavelength absorption	Conjugated double bonds and heavy atom introduction	The length of π-conjugate bonds influences the ability to absorb at redshifted lengths, which is why authors have invested in the synthesis of thiophene- and phenyl-fused BODIPYs, in the introduction of pyrrole rings, and, alternatively, in heavy atoms.	[292,293,294]
Improve singlet oxygen production ability	Halogenation	The inefficient intersystem crossing (ISC) of BODIPYs limits their usefulness in PDT. As for most PS classes, halogenation is a way to improve this photophysical property. Introducing iodine atoms helps the ISC in a more pronounced way than bromination.	[295,296,297]
	Organic metal complexes	Aksakal et al. examined new ruthenium and iridium BODIPY complexes. They discovered that singlet oxygen generation increased by twenty times with ruthenium. Meanwhile, Jana et al. achieved quantum yields of 67% for a cobalt-complexed dye. These and other findings suggest a connection between these complexes and the singlet oxygen production ability.	[298,299,300]
	Anthracene, pyrene, and fullerene conjugation	Callaghan et al. studied several BODIPY dyes with diverse anthracenes and the pyrene group, all showing greater ISC than the phenyl group bearing one. Fullerene derivatives are also effective PSs, producing ROS efficiently with good biocompatibility and easy body clearance.	[301,302]
	Sulfur core-fusion	Thiophene-fused BODIPYs have shown improved singlet oxygen quantum yields (from 4% to 85%). Oscillations in its ability to carry out type II reactions were due to different functional groups introduced in its meso position.	[292]
	BODIPY dimers and trimers	Combining several BODIPY units covalently linked in the same structure can influence properties, namely the increase in the production capacity of singlet oxygen. This effect is shown by Lu et al. for dimeric dyes and by Prieto-Castañeda et al., whose molecular geometry of analogous trimers is also shown to influence this photophysical property.	[303,304]
Targeting specific organelles	Cationic character	Cationic BODIPYs can become more hydrophilic and gain the ability to target mitochondria. They are attracted to the negatively charged inner mitochondrial membrane, accumulating in the mitochondrial matrix through a concentration gradient.	[305,306,307]
	Morpholine group introduction	The introduction of the morpholine into the core of BODIPYs induces their directing to the lysosome organelle. This finding was observed by several research groups in BODIPY dyes, as this group was introduced to the dyes through a linker.	[308,309,310]
	Amphiphilicity and biomolecule mimetize	Wang et al. have designed a phospholipid-mimetizing BODIPY-based fluorescent surfactant with two hydrophobic chains for cell membrane imaging and PDT. Concerning the latter, its effect is induced by damaging the tumor cells’ cytoplasmic membrane.	[311]
Enhance biocompatibility	Aminoacid functionalization	Amino acid conjugation is a practical approach to improving aqueous solubility and ameliorating their biocompatibility and photobiological efficacy. For example, the aspartic acid-modified BODIPY reported by Yu et al. exhibited enhanced aqueous solubility, singlet oxygen generation ability, and a good phototoxicity ratio.	[312]
	Polymer-junction self-assembly	To enhance the biocompatibility of BODIPYs, these molecules can be modified by attaching PEG derivatives or other hydrophilic polymers. This modification helps to reduce non-specific interactions with biomolecules and improves the stability of self-assembled BODIPY-based polymer-conjugated nanoparticles.	[306,313]
Enhance tumor targeting	Polyamine chain introduction	Tumor cells require amine growth factors and regularly exhibit polyamine transporter overexpression. This makes it possible for BODIPY-polyamine molecules to be transported to cancerous cells, which can improve the effectiveness of these tumor-targeting drugs. In addition, these transporters tolerate the uptake of diverse amines, making them a valuable tool for drug delivery.	[314]
	Sugar-conjugate structures	Recent research has revealed that galactose-containing macromolecules can successfully target various types of cancer. Combining lactose with BODIPYs efficiently targets and impacts tumor cells through enhanced recognition and interaction with overexpressed specific receptors.	[315,316]
		Glucose Transporter 1 is often overexpressed in cancer cells, increasing glucose intake and metabolism. As a result, glycosylated BODIPY triangular skeletons were designed by Durán-Sampedro et al. to promote cellular uptake through the Warburg effect.	[317]
	Polysaccharide-conjugate structures	For example, hyaluronic acid (HA) is commonly used as a polysaccharide-based drug carrier since it is water-soluble, has excellent biocompatibility, and is harmless. Chen et al. prepared an HA-BODIPY through an azide linker group that only triggered phototherapeutics inside tumor cells. This behavior is due to its self-assembled form in the extracellular environment; therefore, ROS production is inhibited.	[318]