Table 1.
Examples of actively targeted and stimuli-responsive nanosystems against glioblastoma multiforme (GBM).
| Targeted Receptor/Stimuli | Ligand/Responsive Entity | Carrier (Size) | Drug | Beneficial Outcome | Reference |
|---|---|---|---|---|---|
| Chloride channel and MMP 2 | CTX peptide | CS nanoparticles (<100 nm) | TMZ | Higher uptake (2–6-fold) and IC50 reduction (50–90%) in glioma cell lines (U188, SF767, and GBM6) compared to CS nanoparticles without CTX and free TMZ | [79] |
| LDL | Angiopep-2 | PEG–PCL nanoparticles (<100 nm) | PTX | Improved transport across BBB (2-fold higher than Taxol) | [81] |
| Serine-arginine-leucine (SRL) peptide | Poly(amidoamine) (PAMAM) dendrimer | Plasmid pEGFP | Increased uptake and accumulation of DNA–PAMAM–SRL system in the brain compared with nontargeted systems | [86] | |
| Tissue factor | EGFP–EGF1 fusion protein | PEG–PLA nanoparticles (<150 nm) | PTX | Longer survival time of glioma-bearing mice (27 days) compared to saline group, Taxol group and nontargeted particles (14, 13, 21 days, respectively) | [82] |
| Transferrin receptor (Tfr1, also known as CD17) | Transferrin + modified c[RGDfK] | Micelle (98 nm) | PTX | Longer survival time of mice bearing intracranial U87 MG glioma (39.5 days) compared to PTX-loaded micelle (34.8 days), Taxol (33.6 days), and saline solution (34.5 days) | [83] |
| Acidic pH | Hydrazone bond | MSN | DOX + CPT | Increased drug release at pH 6.5 when compared to pH 7.4, improving the chemotherapeutic effect | [99] |
| Acidic pH | Hydrazone bond | MSN (80 nm) incorporated into neural stem cells | DOX | Tumortropic migration of neural stem cells carrying DOX-loaded MSN in an intracranial U87 xenograft mouse model, resulting in the induction of apoptosis and improvements in survival (41–42 days) compared to PBS (34 days) | [102] |
Key: LDL, low-density lipoprotein receptor; CS, chitosan; TMZ, temozolomide; MMP, matrix metalloproteinases; CTX, chlorotoxin; PTX, paclitaxel; PEG, polyethylenglycol; PCL, poly-ε-caprolactone; TF, tissue factor; EGFP–EGF1, fusion protein derived from factor VII which retains the special binding affinity for TF without inducing coagulation; MSN, mesoporous silica nanoparticles; DOX, doxorubicin; CPT, camptothecin.