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Review
. 2019 May 8;11(5):640.
doi: 10.3390/cancers11050640.

Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Jihye Yoo  1   2 , Changhee Park  3   4 , Gawon Yi  5   6 , Donghyun Lee  7   8 , Heebeom Koo  9   10   11
Affiliations
Review

Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Jihye Yoo et al. Cancers (Basel). .

Abstract

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.

Keywords: active targeting; biodistribution; drug delivery; ligand; nanoparticle; tumor targeting.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Illustration of biological ligands for active targeting of nanoparticle drug carriers.
Figure 1
Figure 1
Antibody-conjugated nanoparticles (NPs). (A) Schematic illustration of antibody-guided avidin-nucleic-acid nanoassemblies (ANANAS) modified with antiepidermal growth factor receptor (EGFR) antibody (cetuximab) for enhancing cancer targeting. (B) Cell viability assay of cetuximab-guided ANANAS in MCF-7 and MDA-MB-231 cell lines. (C) Tumor growth in mice bearing MDA-MB-231 tumors after intravenous injection of cetuximab-guided ANANAS. Reproduced with permission from Reference [18].
Figure 2
Figure 2
Peptide-conjugated NPs. Schematic illustration of RGD-doxorubicin (DOX)-dendri-grafted poly-L-lysine (DGL)-gelatin nanoparticles (GNP) (RDDG NPs) and RGD-metformin (MET)-DGL-GNP (RMDG NPs). (A) Synthetic procedure for RGD-DGL-GNP (RGD NPs). Chemical structure and synthetic procedure for (B) 4-Carboxybenzaldehyde (p-CBA)-MET (pCM) and (C) p-CBA-DOX (pCD). Illustration of the RDDG NPs and RMDG NPs in the tumor microenvironment (D) and their antitumor/anti-inflammatory effects (E). (F) In vivo fluorescence images showing tumor accumulation of NPs with or without RGD ligand. Reproduced with permission from Reference [29].
Figure 3
Figure 3
Aptamer-conjugated nanoparticles (NPs). Scheme of CX-5461-loaded mesoporous silica NPs modified with AS-1411 aptamers to increase nucleoli targeting. Reproduced with permission from Reference [34].
Figure 4
Figure 4
Small molecule-conjugated nanoparticles (NPs). (A) Scheme of phenylboronic acid (PBA)-conjugated dichloro-(1,2-diamino-cyclohexane)-platinum (II) (DACHPt)-loaded micelles (PBA-DACHPt/m) by self-assembly via polymer−metal complex formation. (B) Blood circulation time of intravenously injected DACHPt/m, PBA-DACHPt/m, and oxaliplatin. (C) Tumor accumulation of DACHPt/m and PBA-DACHPt/m in an orthotopic B16F10 mouse model. (D) Tumor volume of orthotopic B16F10 tumors after treatment with oxaliplatin (8 mg/kg), DACHPt/m, or PBA-DACHPt/m (3 mg/kg). (E) Ex vivo fluorescence images showing tumor tissue accumulation of DACHPt/m and PBA-DACHPt/m. Reproduced with permission from Reference [44].
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