Table 1.
Summary of blood cell-based vehicles for brain drug delivery.
| Source of blood cells | Vehicles | Cargo | Strategies | Brain disease and model | Key advances | Ref. |
|---|---|---|---|---|---|---|
| Erythrocyte | Erythrocyte membrane | Dox-loaded PLGA nanoparticles | Neurotoxin-derived peptide for brain targeting Erythrocyte membrane for long circulation DOX-PLGA for drug release |
Glioma | Brain targeting effect, improved survival of glioma-bearing mice and reduced toxicity | Chai et al. (2017) |
| Erythrocyte membrane | Docetaxel nanocrystals | RGD peptide for tumor targeting Cell membrane for long circulation DOX-PLGA for tumor killing |
Glioma | Superior tumor accumulation and enhanced therapeutic efficacy | Chai et al. (2019) | |
| Erythrocyte membrane | miR155-bearing nanogel | Cell membrane prolongs the circulation lifetime M2pep peptide for active targeting miR155 nuclei acid for promotion of cytokine production and shift macrophage and microglia polarization |
Glioblastoma | Active tumor-targeting capability, reprograming of microglia and macrophages from M2 to M1 phenotype, excellent tumor inhibition efficacy and prolonged survival | Gao et al. (2021) | |
| Erythrocyte membrane | Manganous tetroxide nanoparticles | Erythrocyte membrane for high stability, long circulation, and BBB penetration Mn3O4 nanoparticles as antioxidant mimic nanoenzyme T7 peptides for enhancing BBB penetration |
Ischemic stroke/MCAO rats | Distinct therapeutic effect for rescuing neurocytes before and after thrombolysis by oxygen sponge effect and scavenging free radicals | Shi et al. (2020) | |
| Platelet | Platelet membrane | ZL006e-loaded dextran derivative polymeric nanoparticle | Recombinant tissue plasminogen activator for thrombin-triggering Tat peptide for BBB penetration Platelet membrane for long circulating and thrombus targeting ZL006e for neuroprotection |
Ischemic stroke/MCAO rats | Enhanced anti-ischemic stroke efficacy by recovering the cerebral blood supply and protecting neurons of ischemic penumbra | Xu et al. (2019) |
| Platelet nanobubbles | None | Platelet nanobubbles for accurate lesion-targeting and microvascular bio-remodeling of the stroke lesion | Photothrombotic stroke mice | Stroke lesion microvasculature theranostics and reflecting the dynamic structural nature of the recanalization process | Li et al. (2018) | |
| Platelet membrane | l-Arginine and γ-Fe2O3 magnetic nanoparticles | Platelet membranes for long-term stability and targeting to the damaged blood vessel γ-Fe2O3 nanoparticles for magnetic targeting l-arginine for producing NO |
Focal cerebral ischemia mice model | Rapid targeting to ischemic stroke lesions under the guidance of an external magnetic field In situ generation of NO for enhanced vasodilation, recovery of blood flow, and reperfusion of the stroke microvascular |
Li et al. (2020b) | |
| Leukocytes | Monocyte | DOX-loaded nanodiamonds | Monocytes for BBB penetration and GBM infiltration | Glioblastoma | Improved tumor drug delivery efficacy and damage-associated molecular patterns emission | Wang et al. (2018) |
| Monocytes | Cyclic RGD-modified liposomes loaded with trefoil factor 3 | Leukocytes for BBB crossing cRGD for brain targeting |
Depression/olfactory bulbectomy rats | Excellent dual-brain-targeting and enhanced antidepressant effects of trefoil factor 3 | Qin et al. (2015) | |
| Macrophages | Gold-silica nanoshells | Macrophage for BBB crossing | Brain metastases of breast cancer | Active targeting to brain metastases | Choi et al. (2012) | |
| Macrophages | DOX-loaded PLGA nanoparticles | Macrophage for BBB crossing DOX-loaded nanoparticles for tumor therapy |
Glioma | Higher brain tumor distribution of nanoparticles and enhanced anti-glioma effect with prolonged survival | Pang et al. (2018) | |
| Macrophages | Nanocapsule consists of a Dox–silica complex | Macrophage for chemotactic migration Nanocapsule for controlled Dox release and cancer cell killing |
Glioma | Efficient tumor growth suppression and minimal systematic toxicity | Zhang et al. (2018) | |
| Macrophage-derived exosomes | SPIONs and curcumin | Exosomes for BBB crossing Neuropilin-1-targeted peptide for glioma targeting SPION-mediated magnetic flow hyperthermia Curcumin for potent synergistic antitumor therapy |
Glioma | Remarkable synergistic anti-glioma effect between MFH and Cur and extended survival of tumor-bearing mice | Jia et al. (2018) | |
| Macrophage-derived exosomes | Edaravone | Exosomes for brain targeting and improving bioavailability of drug Edaravone for neuroprotection |
Ischemic stroke/permanent MCAO rats | Improved pharmacokinetic parameters and enhanced the bioavailability of edaravone Efficient delivery into the ischemic brain and enhanced neuroprotective effect |
Li et al. (2020a) | |
| Macrophage | Polymer backpacks of catalase | Macrophage for BBB crossing Catalase for attenuating free radicals production |
LPS-induced encephalitis mice model | Recruitment of macrophages with the attached backpacks to the inflamed brain Attenuated oxidative stress from activated microglia |
Klyachko et al. (2017) | |
| Macrophage-derived exosomes | BDNF | Exosomes for BBB crossing BDNF for depression treatment |
LPS-induced encephalitis mice model | Increased concentration of BDNF in inflamed brain | Yuan et al. (2017) | |
| Macrophage-derived exosomes | Catalase | Exosomes for BBB crossing and preserving drug during circulation Catalase for neuroprotection |
6-OHDA mice PD model | Enhanced neuroprotective effects against neurodegeneration | Haney et al. (2015) | |
| Macrophage-derived exosomes | Curcumin | Exosomes for BBB crossing Curcumin to prevent neuronal death |
OA-induced AD murine models | Inhibited Tau phosphorylation, enhanced neuroprotection in AD mice and reversed cognitive dysfunction | Wang et al. (2019) | |
| Neutrophil | PTX-loaded liposomes | Neutrophil for BBB penetration PTX-loaded liposomes for killing residual tumor cells and inhibiting tumor recurrence |
Postoperative glioblastoma by open-window technique | Enhanced BBB penetration, slowed recurrent growth of tumor and improved survival rates | Xue et al. (2017) | |
| Neutrophil-derived exosomes | DOX | Neutrophils for inflammatory chemotaxis and BBB-crossing | Glioma | Efficient suppress of tumor growth and prolong survival | Wang et al. (2021) | |
| Neutrophils | Cross-linked DGL nanoparticles containing cis-aconitic anhydride-modified catalase | Neutrophil-mediated inflammatory migration for BBB penetration and ischemic brain targeting Catalase for ischemic stroke treatment |
Ischemic stroke/MCAO mice | Reduced the infarct volume and inhibited of ROS-mediated apoptosis | Zhang et al. (2017) | |
| Neutrophils and monocytes | cRGD liposomes loaded with edaravone | Neutrophils and monocytes for brain targeting Edaravone for ischemia treatment |
Ischemic stroke/MCAO mice | Enhanced protection against ischemic injury | Hou et al. (2019) | |
| Neutrophil membrane-derived nanovesicles | Resolvin D2 | Neutrophil membrane-derived nanovesicles for inflamed brain targeting Resolvin D2 mitigate neuroinflammation |
Ischemic stroke/ischemia and reperfusion mice | Prevent neurological damage during reperfusion for ischemic stroke therapy | Dong et al. (2019) | |
| Neutrophil membrane | Mesoporous Prussian blue nanozyme | Neutrophil membrane camouflage for BBB penetration and inflamed brain targeting Nanozyme induce microglia M2 polarization and neuron protection |
Ischemic stroke/transient MCAO mice | Relieved ischemic damage and improved neurological function | Feng et al. (2021) |
6-OHDA: 6-hydroxydopamine; AD: Alzheimer’s disease; BBB: blood–brain barrier; BDNF: brain-derived neurotrophic factor; DGL: dendrigraft poly-l-lysine; DOX: doxorubicin; LPS: lipopolysaccharide; MCAO: middle cerebral artery occlusion; OA: okadaic acid; PD: Parkinson’s disease; PLGA: poly(lactic-co-glycolic acid); PTX: paclitaxel; RGD: Arg-Gly-Asp-d-Tyr-Lys; SPIONs: superparamagnetic iron oxide nanoparticles.