Targeting nanoparticle (NP) carriers to sites of disease is critical for their successful use as drug delivery systems. Along with optimization of physicochemical properties, researchers have focused on surface modification of NPs with biological ligands. Such ligands can bind specific receptors on the surface of target cells. Furthermore, biological ligands can facilitate uptake of modified NPs, which is referred to as ‘active targeting’ of NPs. In this review, we discuss recent applications of biological ligands including proteins, polysaccharides, aptamers, peptides, and small molecules for NP-mediated drug delivery. We prioritized studies that have demonstrated targeting in animals over in vitro studies. We expect that this review will assist biomedical researchers working with NPs for drug delivery and imaging.

We fabricated poly (ethylene glycol)-block-polycaprolactone (PEG-b-PCL) nanoemulsion for drug delivery and photodynamic therapy. PEG-b-PCL effectively stabilized the interface between water and soybean oil, and the resulting nanoemulsion was about 220.3 nm in diameter with spherical shape. For photodynamic therapy (PDT), chlorin e6 (Ce6) was loaded into the nanoemulsion as a photosensitizer (PS). These chlorin e6-loaded PEG-PCL nanoemulsions (Ce6-PCL-NEs) showed efficient cellular uptake and, upon laser irradiation, generated singlet oxygen to kill tumor cells. Particularly, Ce6-PCL-NEs showed prolonged blood circulation and about 60% increased tumor accumulation compared to free Ce6 after intravenous injection to 4T1 tumor-bearing mice. These results demonstrate the promising potential of Ce6-PCL-NEs for efficient PDT and in vivo drug delivery to tumor tissue.