Table 1.

Different types of targeting ligands available

Types of ligands	Basic structural elements	Advantages	Disadvantages	Clinical use as targeting ligand	Ref.
Antibodies	Aminoacids (high molecular weight)	Strong binding affinity; High specificity	High production cost; Large size; Immunogenicity	Antibody-drug conjugates approved; NPs with antibodies as targeting ligand in Clinical Trials (SGT-94)	[24–29]
Proteins	Aminoacids (high molecular weight)	High specificity	High production cost; Large size	In Clinical Trials (MBP-426, 2B3-101, CALAA-01, 2B3-101)	[30–34]
Peptides	Aminoacids (low molecular weight)	Simple to produce; Small size; High affinity	May be cleaved by proteases in circulation	In Clinical Trials (BT1718, CEND-1)	[35–38]
Aptamers	Synthetic structural RNA/DNA	High specificity; Small size; Customizable for any target	High production cost; May be cleaved by nucleases in circulation	In pre-clinical development (Sgc8, A-10, AS1411, TTA 1)	[39–44]
Small Molecules	Chemical elements (carbon, oxygen, sulfur, etc.)	Low production cost; Small size	Target specificity reduced	In Clinical Trials (SEL-068, BIND-014)	[23, 45–48]