Table 1.
Strategies for dendrimers to penetrate blood–brain barrier and target brain tumors.
| Drug or Genetic Cargo | Ligand Modification and Targeted Receptors | Other Main Features | Reference |
|---|---|---|---|
| Poly(amidoamine) (PAMAM)-Based Dendrimers | |||
| Doxorubicin | Cationic bovine serum albumin targets negatively charged endothelial cell membranes. | Protonation of free amine groups on dendrimer surface in the acidic environment of tumor tissue. | [105] |
| Nimesulide | - | PAMAM G3 dendrimer, modified with glycidol, and mixed with G0 PAMAM, reduces systemic cytotoxicity. | [111] |
| Apoptin | - | Short peptide chains on dendrimers hydrolyzed by peptidase, facilitate the release of positively charged ions and molecules, disrupt the membrane, resulting in endosomal escape via proton sponge effect. | [112] |
| Celecoxib, Fmoc-L-leucine | Biotin targets cancer cells overexpressing biotin receptors. | - | [106,107] |
| - | Intrinsic targeting ability to activated microglia/macrophages in CNS by hydroxyl-terminated G4 dendrimers. | - | [113] |
| Epirubicin, Let-7 miRNA | - | Positively charged surface with Gd and nanographene oxide used for loading drugs through adsorption and electrostatic interactions for combination therapy. | [114] |
| microRNA 21 (miR-21) inhibitor | - | miR-21 inhibitor loaded dendrimers enhance chemosensitivity of glioblastoma cells to paclitaxel through EGFR/STAT3 signaling. | [115] |
| Polyethylene Glycol (PEG)-Based Dendrimers | |||
| Bortezomib | Cyclo (Arg-Gly-Asp-D-Tyr-Lys) peptide selectively binds the integrin αvβ3 on cell membrane, resulting in integrin-mediated endocytosis. | Sustained drug release by weakening conjugation between bortezomib and dopamine upon acidic stimuli. | [116] |
| Quercetin, acetazolamide, lipoic acid | - | Telodendeimer micelles with covalently linked and physically entrapped drugs for combination therapy. Loading efficiency dependent on the physical fit between the drug and micelle core structure. | [83] |
| pDNA, RNAi | Peptide T7 (His-Ala-Ile-Tyr-Pro-Arg-His) specifically targets brain endothelial and cancer cells overexpressing transferrin (Tf) receptors. | - | [101] |
| PEGylated PAMAM-Based Dendrimers | |||
| Doxorubicin | Angiopep-2 binds low-density lipoprotein receptor-relative protein-1 (LRP1) on the endothelial cells of BBB. EP-1 peptide screened to target epidermal growth factor receptors (EGFRs). | - | [104] |
| Mesenchymal-epithelial transition (MET)-targeting cMBP peptide | Aberrant MET activation targeted which normally associates with invasiveness and drug resistance of gliomas. | - | [117] |
| Cytotoxic peptide KLAK | Dissociation of the matrix metalloproteinase 2 (MMP2)-sensitive peptide triggers PEG deshielding, and leads to exposure of the cell-penetrating peptide. | - | [118] |
| - | Glioma homing peptides (Pep-1) specifically bind the overexpressed interleukin-13 receptors α2 (IL-13Rα2) on glioma cells. | - | [109] |
| Doxorubicin | Tripeptide Arg-Gly-Asp (RGD) can identify and bind the integrin αvβ3 on cell membrane. | - | [108] |
| Dendritic Polyglycerols (dPGS) | |||
| Paclitaxel | Neural cell adhesion molecule (NCAM) overexpression has been found in many tumor cells and correlates with metastasis. | Dendrimer conjugated with NCAM-targeted peptide (NTP) efficiently inhibits endothelial cell migration and offers anti-angiogenesis potential. | [119] |