Table 1.
Ligand-based actively tumor-targeted nanocarriers for the receptor-directed drug-targeting of various types of cancer over the last 10 years of Italian research.
| Ligand | Nanosystem | Conjugation Strategy | Drug/Payload | Receptor | Cancer Type | Ref. |
|---|---|---|---|---|---|---|
| Small molecules | ||||||
| FA | Polymeric NPs (CHIT) | amide bond | MTX | FR | cervical adenocarcinoma | [52] |
| FA | Polymerosomes | amide bond | ds-DNA and ds-siRNA | FR | cervical carcinoma, breast adenocarcinoma | [53,54] |
| FA | Polymeric NPs (DEX) | ester bond | DOX | FR | breast adenocarcinoma breast |
[55] |
| FA | Polymeric NPs (PCL) | amide bond | fluorescent probe (Nile red) | FR | cervical carcinoma, lung carcinoma | [56,57,58] |
| biotin | Micelles | ester bond | niclosamide | biotin receptor | lung carcinoma | [68] |
| biotin | Micelles | ester bond | verteporfin | biotin receptor | prostate cancer, breast adenocarcinoma | [69] |
| TSPO ligands | Polymeric NPs (PLGA) | ester bond | 5-FU | TSPO | glioma | [75] |
| TSPO ligands | G(4)-PAMAM dendrimers | amide bond | fluorescent probe (fluorescein) | TSPO | glioma | [76] |
| lactobionic acid | G(4)-PAMAM dendrimers | amide bond | sorafenib | asialoglycoprotein receptor | liver cancer | [77] |
| alendronate | Polymeric NPs (PLGA) | amide bond | DOX | bone hydroxyapatite | bone cancer | [78] |
| alendronate | PEG dendrimers | amide bond | PTX | bone hydroxyapatite | prostate cancer | [80] |
| FA | SVAs | covalent bond (FA conjugated polyasparthydrazide) | GEM | FR | breast cancer | [129] |
| FA | Liposomes | covalent bond (FA-DSPE conjugate post insertion) | DOX | FR | cervical carcinoma | [130] |
| FA | Liposomes | covalent bond (FA-DSPE conjugate in mixture and post insertion) | a synthetic DOX conjugated with nitric oxide (NO)-releasing group | FR | breast cancer | [131] |
| Peptides and proteins | ||||||
| GNQWFI peptide | Polymeric NPs (PCL) | amide bond | DTX | VEGFR1 | breast adenocarcinoma | [70] |
| GE11 peptide | Polymeric NPs (PLGA) | amide bond | CUR | EGFR | colon adenocarcinoma | [73] |
| GE11 peptide | Polymeric NPs (PLGA) | amide bond | model drug (myoglobin) | EGFR | lung carcinoma | [74] |
| LinTT1 peptide | Liposomes | covalent bond on the surface of preformed liposomes | DOX and sorafenib | p32 protein | breast cancer | [91] |
| NGR motif-containing peptide | Liposomes | covalent bond on the surface of preformed liposomes | BTZ | aminopeptidase N-positive tumor vessels | neuroblastoma | [93] |
| NGR motif-containing peptide | Liposomes | covalent bond on the surface of preformed liposomes | Fenretinide | aminopeptidase N-positive tumor vessels | neuroblastoma | [94] |
| BN(7–14) peptide | Liposomes | amphiphilic peptide derivative mixed with the other lipids | DOX and 111InCl3 | BN receptors | prostate adenocarcinoma | [95] |
| BN-AA1 | Liposomes | amphiphilic peptide derivative mixed with the other lipids | DOX | BN antagonist | prostate cancer | [96] |
| Peptide R | Liposomes | covalent bond on the surface of preformed liposomes | DOX | CXCR4 receptor-antagonist | melanoma lung metastasis | [98] |
| UT-II | Liposomes | covalent bond on the surface of preformed liposomes | DOX | UT-receptor | colon, bladder and prostate cancer | [100] |
| Tf | Liposomes | inserted on the surface of preformed liposome | artemisinin | TfR | colon cancer | [121] |
| Tf | hybrid self-assembling NPs | pre-formed cationic liposomes mixed with Tf | ZOL | TfR | glioblastoma | [124,125] |
| Tf | SNALPs | covalent bond on the preformed NC | miR-34a | TfR | mieloma | [126] |
| Tf | Niosomes | covalent bond on the external surface of the niosomes | DOX | TfR | breast cancer | [127] |
| Tf and FA | Niosomes | covalent bond on the external surface of the niosomes | DOX and CURC or DOX and quercetin | TfR | breast cancer | [128] |
| CPE (Arg4-DAG) | Liposomes | association to the liposome bilayer | model drugs (calcein or BSA) | cervical cancer | [139] | |
| CPE (Arg4-DAG) | Liposomes | association to the liposome bilayer | DOX | breast cancer | [140] | |
| Lf | Liposomes | covalent bond on the surface of preformed liposomes | T3 | multiple receptors | hepatocellular carcinoma | [142] |
| TSH | Nanoliposomes | covalent bond | GEM | TSHR | thyroid carcinoma | [144] |
| ApoE | SLNs | electrostatic interaction | MTX derivative | VLDL | glioblastoma multiforme | [150] |
| Tf/INS | SLNs | covalent bond | MTX derivative | TfR/HIR | glioblastoma multiforme | [151] |
| CKAAKN peptide | SQ NPs | thioether bond | GEM | frizzled receptors | pancreatic cancer | [153] |
| CKAAKN peptide | SQ NPs | thioether bond | GEM | frizzled receptors | pancreatic cancer | [154] |
| Antibodies | ||||||
| rituximab | Polymeric NPs (PLGA) | amide bond | Nutlin-3 | CD20 | chronic lymphocytic leukemia | [71] |
| rituximab | Polymeric NBs (CHIT) | reductive amination | antagomir17 | CD20 | Burkitt limphoma | [86] |
| Anti-CD11c or anti-CD1a monoclonal antibody | Polymeric NBs (CHIT) | reductive amination | plasmid coding for HER2 | murine DC marker CD11c or human DC marker CD1a | breast cancer | [87] |
| anti-Syndecan-1 antibody | Polymeric NPs (PLGA) | amide bond | Nutlin-3 | CD-138/Syndecan-1 | lymphoma | [72] |
| mAb 3F8 | Liposomes | covalent bond on the surface of preformed liposomes | etoposide | anti-GD2 | neuroblastoma, cervical carcinoma, breast carcinoma, melanoma, osteosarcoma | [134] |
| Ab against Frizzled 10 (FZD10) protein | Liposomes | covalent bond on the surface of preformed liposomes | 5-FU | anti-Frizzled 10 protein (FZD10) | colorectal cancer | [135] |
| Hyaluronic acid | ||||||
| HA (HMW)+50:56 | Polymeric NPs (CHIT) | ionotropic gelation | everolimus | CD44 | human mesenchymal stem cells (hMSCs) | [59,60] |
| HA (LMW) | Micelle-like albumin NPs | amide bond | DOX | CD44 | breast adenocarcinoma | [61] |
| HA (HMW) | Polymeric NPs (PLGA) | physical adsorption | sclareol | CD44 | breast cancer | [62] |
| HA (LMW) | Polymeric NPs (PLGA) | layer-by-layer deposition | DTX | CD44 | lung cancer | [63] |
| HA (LMW) | Polymeric NPs (PLGA) | layer-by-layer deposition | 5-FU/plasmid pL3 | CD44 | colon cancer | [64] |
| HA (LMW) | Polymeric NPs (PLGA) | layer-by-layer deposition | DTX/photosensitizer (disulfonate tetraphenyl chlorin) | CD44 | breast cancer and cervix cancer | [65,66] |
| HA (LMW) | Polymeric NPs (PLGA) | layer-by-layer deposition | DTX/photosensitizer (tetrasodium-meso-tetra- (4-sulfonatophenyl)porphyrin) |
CD44 | breast cancer | [67] |
| HA (LMW) | Liposomes | HA-phospholpid conjugate inserted in liposome | GEM lipophilic prodrug | CD44 | pancreatic cancer | [109,110] |
| HA (LMW) | Liposomes | HA-phospholpid conjugate inserted in liposome | diethyldithiocarbamate-copper | CD44 | pancreatic cancer | [111] |
| HA (LMW) | Liposomes | HA-phospholpid conjugate inserted in liposome | synthetic DOX conjugated with a H2S-releasing moiety | CD44 | osteosarcoma | [112] |
| HA oligosaccharides | Liposomes | conjugate inserted in liposome | fluorescently labeled | CD44 | lung cancer | [113] |
| HA (HMW) | Lipoplexes | HA-phospholpid conjugate inserted during lipoplexes formation | plasmid DNA | CD44 | breast cancer | [116] |
| HA (HMW) | Lipoplexes | HA-phospholipid conjugate inserted during lipoplexes formation | plasmid DNA | CD44 | lung cancer | [117] |
| HA (HMW) | Lipoplexes | HA-phospholipid conjugate inserted during lipoplexes formation | anti-telomerase siRNA | CD44 | lung cancer | [118] |
| HA (HMW) | Lipoplexes | HA-phospholipid conjugate inserted during lipoplexes formation | anti-Luc siRNA | CD44 | metastatic lung cancer | [119] |