Table 2.
Targets and targeting moieties used in the design of targeted liposomal drug carriers for the treatment of breast cancer with associated in vitro and in vivo cell lines.
| Target type | Target | Targeting entity | Application | + Cell line used | - Cell line used | References |
|---|---|---|---|---|---|---|
| CELL SURFACE RECEPTORS | ||||||
| Chemokine Rc | CXCR4 | CXCL12/SDF-1 | MBC, TNBC | HCC1500, MDA-MB-175VII, MDA-MB-436, MDA-MB-231, 4T1 | MCF-10A, MCF-7 | [[114], [115], [116], [117]] |
| Cell surface nucleosomes | Antinuclear Abs | mAb 2C5 | Breast cancer, luminal, MDR, TNBC | BT-20, MCF-7, MDA-MB-231, SK-BR-3, 4T1 | [[118], [119], [120], [121]] | |
| Eph Rc | EphA2 | Anti-EphA2 scFv, YSA peptide |
TNBC, MBC | BT-549, MDA-MB-231, SUM-149PT, EMT-6 | MCF-7/S0.5 | [[122], [123], [124]] |
| Folate Rc | FRα | Folate, FA | MBC, MDR, TNBC | MDA-MB-231, MCF-7, MCF-7/ADR*, SK-BR-3, T-47D, 4T1, TUBO | MCF-10A, MCF-7, A549, JC, L929 | [[125], [126], [127], [128], [129], [130], [131], [132], [133]] |
| ICAM-1 | ICAM-1 | ICAM-1 Ab | TNBC | MDA-MB-231 | MCF-10A | [134] |
| LDL Rc-related protein | LRP1 | Angiopeptide LRP1 ligand | Breast cancer | MT-3c) | [135,136] | |
| Nucleolin | Nucleolin | F3 peptide, AS1411 aptamer | Breast cancer, TNBC, MDR | MDA-MB-231, Hs578T, MDA-MB-435Sb), MDA-MB-231-derived CSCs, MCF-7/ADRa) | T-47D, MCF-7, MCF-7-derived CSCs, MCF-10A, CHO | [[137], [138], [139], [140], [141], [142], [143]] |
| P-gp | P-gp, VM channels | TPGS | MDR | MDA-MB-435Sb), MCF-7, MCF-7/ADRa) | [[144], [145], [146]] | |
| Somatostatin receptor | Somatostatin receptor-2 | Octreotide, somatostatin analogs | Breast cancer, MBC, TNBC | MDA-MB-231, MDA-MB-436, MCF-7, MDA-MB-435Sb), MCF-12A | [[147], [148], [149]] | |
| Sigma Rc | Sigma-1 Rc, Sigma-2 Rc | Haloperidol, SV119 | Breast cancer | MCF-7 | HeLa, KB, HepG2, BEAS-2B, CHO | [150,151] |
| TfR | TfR1 | Transferrin | Breast cancer, luminal | MCF-7 | [152,153] | |
| uPA | uPAR | PAI-2 | TNBC, MBC | MDA-MB-231 | MCF-7 | [[154], [155], [156]] |
| TRANSMEMBRANE RECEPTORS | ||||||
| Biotin | SMVT | Biotin | Breast cancer, Luminal | MCF-7, 4T1 | B16, L929 | [[157], [158], [159]] |
| CD44 Rc | CD44 | HA | MBC, TNBC, Luminal | MDA-MB-231, MDA-MB-231-derived CSCs, MCF-7 CSCs, 4T1 | MCF-7, A549 | [[160], [161], [162], [163], [164], [165]] |
| HER Rc | HER1 | CET, anti-HER1 aptamers | TNBC | SK-BR-3, MDA-MB-468, MDA-MB-231, BT-20 | MCF-7, MDA-MB-453 | [[166], [167], [168]] |
| HER Rc | HER2 | Trastuzumab, HER2 Fab’ fragments, VHH, affibodies, tumor-targeting peptides | Breast cancer, luminal | SK-BR-3, HCC1954, BT‐474, MTSV1-7, MCF-7/Her18, TUBO | MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF-10A, MCF-7, MCF-12A, Calu-6, A549, cE2 | [[169], [170], [171], [172], [173], [174], [175], [176], [177], [178], [179], [180], [181], [182], [183], [184], [185], [186], [187], [188], [189]] |
| Integrin Rc | αvβ3, αvβ1, αvβ1, αvβ5, VM channels | RGD, R8GD, cRGD fibronectin-mimetic peptide-amphiphile PR_b | Breast cancer, luminal A, CSCs, TNBC | MCF-7/ADRa), MDA-MB-435Sb), MDA-MB-468, HCC1806, MDA-MB-231, MDA-MB-231-derived CSCs, 4T1 | MCF-7, MCF-10A | [[190], [191], [192], [193], [194], [195], [196], [197]] |
| LHRH Rc | LHRH Rc | Gonadorelin | Breast cancer | MCF-7 | SK-OV-3 | [198,199] |
| MUC1 | Tumor-associated-MUC1 | hCTMO1, MUC1 antigenic peptide, MUC1 aptamer | Breast cancer, TNBC, Luminal | MDA-MB-435, MCF-7, 4T1 | MCF-10A, C33a, HepG2 | [[200], [201], [202], [203]] |
| NRP1 | NRP1 | A7RC peptide, PTD-3, TAT-PTD | Breast cancer, TNBC | MDA-MB-231, 4T1 | MCF-7, SUIT-2 | [204,205] |
| INTERNAL CELL RECEPTORS | ||||||
| Estrogen Rc | ERα | E1, E2, E3 | Luminal, ER+ | MCF-7, T-47D, ZR-75-1 | MDA-MB-231, HCC-1954 | [[206], [207], [208], [209], [210], [211]] |
| ENZYMES | ||||||
| MMP | MMP-2, MMP-9 | Chlorotoxin peptide, EGCG | MBC, breast cancer | MDA-MB-231, 4T1 | [212,213] | |
| Phospholipases | sPLA2 | sPLA2-triggered release | MBC, TNBC | MT-3c) | [214] | |
Cell line inclusion criteria: Breast cell lines included which expressed (i.e., +) the target and cell lines that did not express (i.e., -) the target according to the referenced literature. Cell lines that expressed the target but did not originate from breast tissue were not included. Negative controls not originating from mammary tissue are indicated in red, and rodent cell lines are underlined. It should be noted, that some articles indicated that the negative control cell lines used did express the targeted moiety but at ‘non-high expression’ levels.
Abs: antibodies; anti-EphA2 scFv: anti-erythropoietin-producing hepatocellular single-chain variable fragment; CD44: cluster of differentiation 44; CET: cetuximab; CSCs: cancer stem cells; CXCR4: C-X-C chemokine receptor type 4; CXCL12/SDF-1: CXCR4 receptor ligand; E1, E2, E3: estrone, estradiol, estriol; EGCG: epigallocatechin gallate; Eph: erythropoietin-producing hepatocellular receptor; EphA2: erythropoietin-producing hepatocellular receptor A2; ER+: expression of estrogen receptor; ERα: estrogen receptor α; FA: folic acid; Fab’: fragment antigen-binding with the addition of a thiol group; FRα: folate receptor α; HA: hyaluronic acid; hCTMO1: humanized anti-mucin 1 monoclonal antibodies; HER: human epidermal receptor; ICAM-1: intracellular adhesion molecule-1; LHRH: luteinizing hormone-releasing hormone; LRP1: low density lipoprotein receptor-related protein 1; MBC: metastatic breast cancer; MDR: multidrug resistant; MMP: matrix metalloproteinases; MUC1: mucin 1; NRP1: neuropilin 1; PAI-2: plasminogen activator inhibitor-2; P-gp: p-glycoprotein; Rc: receptor; RGD: arginylglycylaspartic acid, Arg-Gly-Asp; sPLA2: secretory phospholipase A2; SVMT: sodium-dependent multivitamin transporter; TfR: transferrin receptor; TNBC: triple negative breast cancer; TPGS: D-α-tocopheryl polyethylene glycol 1000 succinate; uPA: urokinase-type plasminogen activator; uPAR: urokinase-type plasminogen activator receptor; VHH: variable domain of the heavy chain antibody; VM: vascular mimicry.
Contaminated/misidentified cell line; renamed NCI/ADR-RES, possibly derived from OVCAR-8 [215].
Problematic cell line, derived from melanocytes [216].
Problematic cell line, contaminated with LS-174T cells.