Table 2.
IONs decorated with targeting agents for their internalization through receptor-mediated endocytosis in their target tissue.
| Target | Main Endocytic Mechanism(s) | Targeting Agent | Coating | Target Cells | Application | Ref |
|---|---|---|---|---|---|---|
| LOX-1 receptor | Clathrin- and caveolin-independent [212] | LOX-1 antibody | Poly(ethylenglycol) (PEG) | Activated foam macrophages | Imaging probe for detecting early diabetic nephropathy (DN) | [213] |
| OxLDL | anti-OxLDL-PEG | Activated foam macrophages | Imaging of atheroschlerotic plaque lesions | [214] | ||
| Transferrin receptor (TFR) | Clathrin-dependent | Transferrin | Dimercaptosuccinic acid (DMSA) | C6 | Imaging probe for glioma | [184] |
| Ammoniated glucose-oligosaccharides-FITC | 4T1 | Not specified | [185,186] | |||
| Chitosan/Doxorubicin (DOX) | U251 | Drug delivery | [187] | |||
| Dextran-spermine | BBB (in vivo) | Drug delivery in vivo | [215] | |||
| Poly-L-lisine | HeLa | Not specified | [216] | |||
| RI7217 monoclonal antibody | DSPE-PEG-Muscone/Cholesterol/EPC liposomes | BBB and U87-MG in vivo (Mice) | Drug delivery in vivo | [217] | ||
| OX26 monoclonal antibody | Soy PC/DDAB/mPEG2000-PE liposomes | Rat BCECs in vitro and rat BBB in vivo | Targeted delivery to the brain | [218] | ||
| EGF receptor | Clathrin-dependent, Caveolin-dependent, Clathrin-and caveolin-independent | EGF | Amino-dextran | C6 | Cancer imaging probe | [188] |
| Carboxymethyldextran (CMD) | Caco-2 | Not specified | [219] | |||
| Nibotuzumab | Silica | A431 | Not specified | [191] | ||
| Cetuximab | PEG-dextran | A431 | Imaging probe | [190] | ||
| Short-chain EGFR antibody fragments (ScFv) | Poly(ethylene oxide)-poly(γ-methacryloxypropyl trimethoxysilane) | SK-BR-3 & MDA-MB-231 | Imaging probe | [192] | ||
| VEGF receptor | Clathrin-dependent, Caveolin-dependent | Bevacizumab | PEO-b-PγMPS-NIR830 | 4T1 | Imaging probe | [193] |
| Anti-VEGF | Poly(aspartate)-g-poly(ethylene glycol)-dodecylamine-hydrazone-(adriamycin-levulinic acid) micelles | HepG2 | Imaging probe | [194] | ||
| Human epidermal receptor 2 (HER-2) | Clathrin-dependent | Trastuzumab | PEG-SH | SK-BR-3 | Drug delivery | [195] |
| Anti-HER2 affibody | Polybutylacrylate-polyethylacrylate-polymethacrylic acid-NIR830 | SKOV3 | Imaging probe | [196] | ||
| Folate receptor | Clathrin- and caveolin-independent | Folate | PEG | U87-MG | Chemotherapy and hyperthermia | [200] |
| No additional coating | 22Rv.1, LnCaP | Imaging probe and hyperthermia treatments | [220] | |||
| Polyethilenimine (PEI) | KB | Imaging probe | [201] | |||
| PEG-poly(e-caprolactone) | BEL-7402 | Tumor imaging | [221] | |||
| LRP1 | Clathrin-dependent | Lactoferrin | Poly(maleic anhydride-alt-1-octadecene) (PMAO) | C6 | Imaging of brain glioma | [222] |
| Angiopep-2 | Pluronic-poly(acyrlic acid) (PF12-PAA) | BMECs | Delivery to the brain | [223] | ||
| CD44 | Clathrin- and caveolin-independent Clathrin-dependent [199] | Hyaluronic acid | Hyaluronic acid-C16 | MDA-MB-231, NIH/3T3 | Cancer imaging and therapy | [202] |
| Anti-CD44 | DMSA | Panc-1, MBA-MB-231 | Cancer therapy | [205] | ||
| CMD | HNSCC | Cancer hyperthermia | [203] | |||
| IGF1 receptor | Clathrin-dependent, Caveolin-dependent | IGF1 | Amphiphilic polymer | MIAPaCa-2 | Drug delivery in vivo | [224] |
| Anti-insulin-like-growth-factor binding protein 7 (anti-IGFBP7) | Dextran-Cy5.5 | BBB and U87 MG in vivo | Imaging probe | [225] | ||
| uMUC-1 | Clathrin-dependent | EPPT1 | Streptavidin-conjugated dextran | 6606PDA (Mouse) | Cancer theranostic platform | [207] |
| Membrane-bound matrix metalloproteinase (MMP-2) | Clathrin-dependent, Caveolin-dependent [226] | Chlorotoxin | PEG-g-chitosan/PEI | C6 | Imaging probe and siRNA delivery to cancer cells | [136] |
| Carbonic anhydrase IX (CA-IX) | Caveolin-dependent [227] | M75 monoclonal antibody | Poly-L-lysine (PLL) | CA-IX cDNA-transfected C33a cells | Targeting of hypoxic cells (Cancer) | [208] |
| CD22 | Clathrin-dependent [228] | Anti-CD22 | Amphiphilic polymer/PEI | preB-ALL | Cancer therapy for preB-ALL cells | [209] |
| Cholecytoskinin-2 receptor (CCK2R) | Clathrin-dependent | CCK | DY647-PEG | HEK293 stably expressing CCK2R | Cancer therapy | [229] |
| αvβ3 integrin | Clathrin-dependent, Caveolin-dependent, Clathrin- and caveolin-independent [230] | RGD peptide | PEG | U87 MG | Imaging probe and drug delivery in vivo | [210] |
DSPE: 1,2-Distearoyl-sn-glycero-3-phosphorylethanolamine; EPC: 1,2-distearoyl-sn-glycero-3-ethylphosphocholine; PC: L-α-phosphatidylcholine; DDAB: dimethyldioctadecylammonium bromide; mPEG2000-PE: 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000; C6: Brain glioma; 4T1: Breast cancer; U251: Human glioblastoma astrocytoma; BBB: blood-brain barrier; HeLa: Human cervical adenocarcinoma; U87-MG: Brain glioblastoma; BCECs: brain capillary endothelial cells; Caco-2: Colorectal adenocarcinoma; A431: Epidermoid carcinoma of vulva; SK-BR-3: Breast carcinoma; MDA-MB-231: Breast carcinoma; HepG2: Human hepatocellular carcinoma; SKOV3: Human ovarian cancer; 22Rv.1: Primary prostate cancer cells; LnCaP: Lymph node metastasis of prostate cancer cells; K8: Cervical carcinoma infected with Human papillomavirus; BEL-7402: Human hepatocellular carcinoma contaminated with human papillomavirus-related endocervical carcinoma; BMECs: Brain microvascular endothelial cells; NIH/3T3: Breast carcinoma; Panc-1: Pancreas/duct epithelioid carcinoma; HNSCC: Head and neck squamous cell carcinoma; MIAPaCa-2: Human pancreatic cancer; 6606PDA: Mouse pancreatic ductal adenocarcinoma; C33a: Human cervical cancer; PreB-ALL: Precursor B-cell acute lymphoblastic leukemia; HEK293: Human embryonic kidney cells.