Table 2. . Biomaterial-based targeting agents that have been utilized to target endothelial cells in the treatment of glioblastoma.
| Target on biomaterial | Target on cell | Endothelial cells used in vitro and in animal models | Biomaterial | Bioactive factor | Outcome | Ref. |
|---|---|---|---|---|---|---|
| Monoclonal antibody | ||||||
| Anti-CD105 antibodies | Endoglin/CD105 |
In vitro: mouse endothelial cell line MS1 and mouse breast cancer cell line 4T1 In vivo: mouse subcutaneous U87MG GBM model |
Perfluorocarbon-containing lipid-shelled MBs for ultrasound contrast agents | None, contrast agent |
In vitro: attachment numbers of the CD105-targeted MBs significantly correlated with the CD105 expression levels of the cells in the parallel flow chamber test In vivo: there was a good correlation between the in vivo molecular ultrasound signals with the CD105-targeted MBs and the ex vivo expression levels of CD105 |
[205] |
| Peptides | ||||||
| cRGD and IL-13 peptide |
αvβ3 integrin on neovasculature |
In vitro: HUVECs In vivo: mouse intracranial C6 GBM model |
PEG-PCL NPs | DTX |
In vitro: IRNPs had high uptake into HUVEC cells In vivo: IRNPs had higher localization in the GBM site than mono-modified NPs |
[43] |
| cRGDyC | αvβ3 | In vitro: HUVECs | Liposomes formed with DPPG, cholesterol, DSPE-mPEG2000 and DSPE-PEG2000-MAL in chloroform and methanol | BSH | In vitro: cRGDyC liposome uptake was significantly higher than plain liposomes in integrin αvβ3-positive HUVEC and U87MG cells | [206] |
| iNGR (CRNGRGPDC sequence) | APN/CD13 |
In vitro: HUVECs In vivo: mouse intracranial U87MG GBM model |
Liposomes made with HSPC, cholesterol and PEG (2000)-DSPE | Dox |
In vitro: Uptake of iNGR-SSL by U87MG cells and HUVECs was significantly greater than that of unmodified liposomes In vivo: accumulation of iNGR-SSL/DiR was significantly increased compared with unmodified liposomes |
[207] |
| iNGR | APN/CD13 |
In vitro: HUVECs In vivo: mouse intracranial U87MG GBM model |
Poly (ethyleneglycol)-poly (L-lactic-co-glycolic acid) NPs | PTX |
In vitro: iNGR-NP-PTX inhibited tube formation more efficiently than unconjugated NPs In vivo: iNGR-NP exhibited the highest fluorescence intensity in the brain compared with other NPs tested |
[208] |
| NGR ligand | APN/CD13 |
In vitro: primary rat BCECs In vivo: mouse intracranial C6 GBM model |
PDA-coated mesoporous silica NPs (MSNs) | Dox |
In vitro: MSN-DOX-PDA-NGR had higher intracellular accumulation in primary BCECs and C6 cells than nontargeting NPs In vivo: MSN-DOX-PDA-NGR had higher accumulation in intracranial tumor tissue than undecorated NPs |
[209] |
| CGKRK (Cys-Gly-Lys-Arg-Lys) | Heparan sulfate on neovascular endothelial cells |
In vitro: HUVECs In vivo: mouse intracranial C6 GBM model |
PEG-PLGA NPs | PTX |
In vitro: cellular fluorescence intensities of CGKRK-NP and PC-NP were significantly higher at various concentrations and all experiment time points compared with normal NPs In vivo: PC-NP (CGKRK and Pep 1) exhibited the most accumulation in glioma |
[210] |
| CGKRK peptide | Heparan sulfate |
In vitro: HUVECs and U87MG cells In vivo: mouse subcutaneous U87MG GBM model |
PEG-co-PCL NPs | PTX |
In vitro: fluorescence intensity of CGKRK-NP on both HUVEC and U87MG cells was significantly enhanced when compared with that of NPs In vivo: following CGKRK-NP-DiR injection, mice exhibited a much stronger fluorescence intensity at the tumor site at every imaging time when compared with that of the NP group |
[211] |
| Tf and PFVYLI (PFV) | TfR | In vitro: bEnd.3 brain endothelial cells | Liposomal NPs made from DOTAP, DOPE, NHS-PEG(2000)-DSPE and cholesterol |
Dox and Erlo | In vitro: Tf-PFV liposomes showed significantly higher cellular uptake compared with single ligand or plain liposomes | [212] |
APN: Aminopeptidase N; BCEC: Brain capillary endothelial cell; BSH: Sodium borocaptate; cRGD: Cyclic Arg-Gly-Asp; cRGDyC: Cyclic Arg-Gly-Asp-Tyr-Cys; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane chloride; DPPG: 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol); Dox: Doxorubicin; DTX: Docetaxel; Erlo: Erlotinib; GBM: Glioblastoma multiforme; HSPC: Hydrogenated soy phosphatidylcholine; HUVEC: Human umbilical vein endothelial cell; MB: Microbubble; NGR: Asp-Gly-Arg; NHS-PEG(2000)-DSPE: 3-(N-succinimidyloxyglutaryl) aminopropyl, polyethyleneglycol-carbamyl distearoylphosphatidyl-ethanolamine; NP: Nanoparticle; PDA: Polydopamine; PEG-PCL: Polyethylene glycol–poly(ε-caprolactone); PEG-PLGA: Polyethylene glycol–poly[(d,l)-lactide-co-glycolide]; PTX: Paclitaxel; Tf: Transferrin; TfR: Transferrin receptor.