Table 5.
The strategies, including achievements and limitations in targeted delivery of nanomedicines in reducing oxidative stress.
| Phase of cascade | Target | Nanomedicine and intervention strategy | Achievement | Limitation | Ref. |
|---|---|---|---|---|---|
| Oxidative stress | |||||
| Small molecule antioxidants | Passively | Curcumin-loaded PLGA NPs | Prevented neurons from oxidative damage | No experimental data in vivo | 121,122 |
| Passively | Curcumin-loaded PEG-PLA NPs | Protected the BBB against oxidative stress; ameliorated neuronal apoptosis and the release of inflammatory mediators. | Conjugating with targeting ligand might further improve the treatment effect | 62 | |
| Bypass the BBB | Curcumin-loaded embryonic stem cell exosomes | Delivered drug into brain intra-nasally, decreased the level of ROS | The safety of nasal administration has not been investigated | 96 | |
| Integrin αvβ3 | Curcumin-loaded exosomes modified with cRGD | Downregulated activated microglia and the expression of inflammatory cytokines | 81 | ||
| Passively | Resveratrol-loaded albumin NPs | Reduced oxidative stress and the apoptosis of neurons | Passive targeting might not be suitable for long-term administration | 61 | |
| AMT | Tanshinone-loaded PEG-PLA NPs conjugated with cationic BSA | Inhibited the inflammatory cascades | There is risks of being phagocytized by the RES | 95 | |
| Passively | Baicalin-loaded liposomes | Improved the accumulation of drug in the ischemic brain | Non-PEGylated liposomes were mainly phagocytized by the RES | 63 | |
| Passively | Luteolin-loaded PEG-PLGA micelles | Inhibited oxidative stress and decreased the release of inflammatory mediators | Targeting efficiency might need further improvement | 64 | |
| LRP | Puerarin-loaded PBCA NPs coated with polysorbate 80 | Reduced the infarct volume | 74 | ||
| A2AR BBB modulation | Edaravone-loaded PEG-PLA micelles modified with CGS21680 | Exerted a more persistent ROS eliminating effect and rescued more neurons | The safety of BBB modulator needs further study | 71 | |
| Passively | PEG-b-PCMS-TEMPO micelles | Suppressed oxidative stress and apoptosis, protected neurovascular units | The study did not reveal the effect and toxicity of NPs in subacute phase | 65,66 | |
| Passively | Melanin-loaded NPs conjugated with PEG | Showed antioxidative effects against multiple RONS, suppressed the expression of inflammatory cytokines | The potential toxicity of the degradation byproducts of PEG-MeNPs needs further investigation | 67 | |
| Antioxidase | NMDAR1 | SOD-loaded liposomes, PBCA NPs, and PLGA-NPs; nanomedicines were modified with anti-NMDAR1 antibody | Reduced the oxidative stress and apoptosis, and inhibited the release of inflammatory mediators | The effect of administration in subacute phase is not satisfactory | 82 |
| Passively | CAT/SOD-loaded PLGA-NPs | Mitigated apoptosis and inflammatory response; promoted neurogenesis | Carotid injection is not conducive to long-term administration | 68 | |
| Biomimetic targeting | PEG-DGL-CAT NPs decorated with PGP, which could hitchhike the circulating neutrophils | Reduced the infarct volume via anti-oxidative effect | The fate of NPs in neutrophils needs further investigation | 91 | |
| Inorganics | Passively | PEGylated ceria NPs | Scavenged ROS and reduced apoptosis | Targeting ability need further improvement | 69 |
| Integrin αvβ3 | PEGylated Ce-NPs conjugated with biotinylated-LXW7 | Showed better effects in mitigating the oxidative stress and apoptosis | There was no improvement in neurological function | 83 | |
| LRP | Edaravone-loaded Ce-NPs modified with angiopep-2 | Exerted synergistic ROS scavenging ability | 84 | ||
A2AR, adenosine 2 A receptor; BSA, bovine serum albumin; LRP, lipoprotein receptor-related protein; RONS, reactive oxygen and nitrogen species.