Table 3.
Recent research on nanoparticles (inorganic materials and organic materials) to overcome BBB in the treatment of CNS diseases.
| Surface modify | Targeting ligands | Receptors | Model drug | Use | Others | Refs |
|---|---|---|---|---|---|---|
| Prussian blue/polyamidoamine (PAMAM) dendrimer/Angiopep-2 (PPA) nanoparticles | A2 | LRP1 | Prussian blue | AD | PPA NPs have superior BBB penetration and are able to exert a synergistic effect of ROS scavenging and restoring mitochondrial function in microglia. PPA NPs effectively reduced the neurotoxic Aβ aggregates and rescued the cognitive function of APP/PS1 mice. | [194] |
| Lacosamide- gold nanoparticles (LCM-AuNP) | glucose | GLUT1 | LCM | epilepsy | The binding of LCM to AuNP not only inhibited seizure activity but also reduced the dosage of antiepileptic drugs. | [195] |
| CTHG-Lf NPs | Lf | LfR | TMZ | glioma | CTHG-Lf NPs is an intelligent BBB permeable nano platform with hollow mesoporous copper sulfide nanoparticles (HM-CuS NPs) as TMZ carrier and hyaluronic acid (HA) as gatekeeper. Further modified with glucose oxidase (GOx) and Lf to achieve efficient synergistic treatment of in situ GBM. | [196] |
| siRNA-loaded synthetic protein nanoparticles (SPNPs) | iRGD | SPARC34/GP60 | STAT3 siRNA | GBM | Sirna-spnps equipped with the cell-penetrating peptide iRGD, capable of delivering siRNA STAT3, were able to improve the survival of GBM mouse models. | [197] |
| rotigotine-loaded chitosan nanoparticles (RNPs) | / | / | rotigotine | PD | Delivery of RNPs by ID enhanced brain targeting efficiency and drug bioavailability. | [198] |
| dodecamer peptide (G23)-functionalized polydopamine (pD)-coated curcumin-loaded zein nanoparticles (Cur-ZpD-G23 NPs) | / | / | Cur | GBM | Cur-ZpD-G23 NPs increased cellular ROS production and induced apoptosis in glioma cells. | [199] |
| integrin α2β1-targeting H-ferritin (2D-HFn)-based drug delivery system | H-ferritin | TfR1 | ntegrin α2β1 | glioma | 2D-HFn not only significantly improved DOX drug loading capacity, but also improved BBB penetration and brain targeting ability. 2D-HFn loaded with DOX significantly inhibited subcutaneous and orthotopic tumor progression and prolonged survival in the orthotopic glioma mouse model. | [200] |
| PLGA functionalized magnetic Fe3O4 nanoparticle (MNP) with L-carnosine peptide (LMNP) composite loaded with dexamethasone (dm@LMNP) | / | / | dexamethasone | ischemic stroke | L-carnosine functionalized iron oxide nanoparticles loaded with dexamethasone can not only improve BBB permeability but also improve the therapeutic effect of ischemic stroke. | [201] |
| Fe3O4 nanozymes | / | / | / | Cerebral ischemic stroke | dietary PEG-modified Fe3O4 nanozymes can facilitate blood–brain-barrier reconstruction and protect neurons following ischemic stroke. | [85] |
| a macrophage loaded with a photothermal nanoprobe (MFe3O4-Cy5.5) | / | / | / | glioma | Fe3O4-Cy5.5 can perform fluorescence, photoacoustic and magnetic resonance imaging, which can be used for precise tumor resection. It can also effectively induce local photothermal therapy and inhibit postoperative glioma recurrence. | [202] |
| DOX- ethylenediamine triacetic acid- iron oxide nanoparticles (DOX-EDT-IONPs) | / | / | DOX | GB, | The combination of magnetically enhanced convective diffusion and cadherin-binding peptides to transiently open the BBB TJ is expected to improve the efficacy of GBM chemotherapy using DOX-EDT-IONPs. | [203] |
| Tween 80- rhynchophylline loaded methoxy poly -poly nanoparticles (T80-NPS-RIN) | apolipoprotein E | LRPs | RIN | AD | T80-NPS-RIN has an enhanced therapeutic effect on nerve injury, with higher brain RIN accumulation concentration and higher bioavailability. | [204] |
| Chiral gold nanoparticles (Chiral AuNPs) | chiral GSH ligand | GSH transporters | / | AD | D3.3 AuNPs have greater binding affinity for Aβ42 and higher brain biodistribution, thereby having A stronger inhibitory effect on Aβ42 fibrillation in AD model mice. | [205] |
| angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) | A2 | LRP1 | PTX | glioma | ANG-LP-MSN-PTX can promote the passage of PTX through the BBB and induce more apoptosis of glioma cells, which is a promising targeted delivery system in the treatment of glioma. | [206] |
| angiopep-2-lipid-based magnetic nanovectors + nutlin-3a (A2-LMNVs + Nut-3a) | A2 | LRP1 | nutlin-3a | GBM | A2-LMNVs have a strong affinity for GBM cells with respect to other healthy cell lines. | [207] |
| ultra-small, large pore silica nanoparticles (USLP)-Lf + DOX | Lf | LfR | DOX | GBM | USLP-Lf enhanced the efficacy of DOX-mediated apoptosis in GBM cells. | [208] |
| monoclonal antibodie (mAb)-conjugated human apoferritin (HFn) nanoparticles (mAb-HFn) | Tf | TfR1 | Trastuzumab (TZ); Cetuximab (CTX) | brain malignancies (such as GBM) | Hfn-conjugated TZ and CTX are promising treatments for brain cancer. | [209] |
| a ROS-responsive ruthenium nanoplatform (R@NGF-Se-Se-Ru) | / | / | NGF | AD | R@NGF-Se-Se-Ru has the ability to inhibit Aβ aggregation and has the potential to be A multifunctional drug for the treatment of AD. | [210] |
| internalized RGG/TGN- polyethylene glycol- poly(amidoamine) dendrimer- Arsenic trioxide (iRGD/TGN-PEG-PAMAM-ATO) | TGN; iRGD | neuropilin-1 receptor; αvβ/αvβ5 | ATO | glioma | Functional conjugation of PAMAM to PEG can reduce the potentially harmful effects of PAMAM, reduce its clearance in the blood, and prolong its retention time in the circulation. Enhancing BBB crossover efficiency and enhancing anti-tumor efficacy, thus showing great potential for glioma treatment. | [211] |
| ultra-small, large pore silica nanoparticles (USLP)-NH2-PEG-TMZ | Lf | LfR | TMZ | GBM | USLP-NH2-PEG-TMZ is effective in blood extravasation and penetration of the BBB and has the potential to improve the efficacy of TMZ in the treatment of GBM. | [212] |
| Yb3+ and Er3+ double-doped CeO2–x upconversion nanoparticles (Yb/Er/CeO2–x UCNPs) | / | / | Yb/Er/CeO2–x | PD | Yb/Er/CeO2–x UCNPs cross the blood–brain barrier and exhibit biocompatibility and antioxidant catalytic properties, which decrease the ROS and effectively help in treating PD. | [213] |
| TGN-CGA@SeNCs | lipopolysaccharide (LPS) | LPS receptor | chlorogenic acid (CGA) | AD | TGN-CGA@SeNCs is a novel flowerlike selenium nanocluster (TGN-CGA@SeNCs) prepared using a brain-targeting peptide (TGN peptide) and CGA, which is able to improve the bioavailability of CGA and reduce the dose of CGA to prevent AD progression. | [214] |
| a Fe3O4 magnetic nanoparticles modified through the growth of Fe-based Metal-organic frameworks of the Materials Institute Lavoiser (MNPs@MIL) + TMZ | / | / | TMZ | GBM | The use of TMZ-loaded MIL@MNPs improved the efficiency of TMZ delivery in the brain. | [215] |
| LCM-AuNP | glucose | GLUT1 | LCM | epilepsy | Lcm-aunp can overcome the BBB and efficiently deliver LCM into the brain parenchyma at an effective dose to reduce seizure severity and frequency in a rat model of KA-induced TLE. | [216] |
| peptide-functionalized gold nanoparticles (Pep-AuNPs) | heptapeptide NIDPNAV | lysophosphatidylcholine | AuNPs | MS | Pep-AuNPs were modified using heptapeptide NIDPNAV that binds specifically to the demyelinating region. Subsequently, intravenous delivery of peptide-modified gold nanoparticles has enhanced the ability to target lesions in the brain, and is more effective in anti-inflammatory and neuroprotection. | [217] |
| levetiracetam-loaded albumin nanoparticles- polysorbate 80 (LEV-NPs-PS 80) | / | / | LEV | epilepsy | LEV-NPs-PS 80 minimized side effects, especially peripheral side effects. In addition, there is an increase in the duration of anticonvulsant activity. | [218] |
| Angiopep-2-conjugated FeTi@Au core-shell nanoparticles (FeTi@Au-A2 NPs) | A2 | LRP1 | FeTi@Au-A2 NPs | glioma | FeTi@Au-A2 NPs hold great promise as a targeted delivery strategy for glioma treatment using hyperthermia. | [219] |
| MNP@BQR@A2-EXO-siGPX4 | A2 | LRP1 | siGPX4 | GBM | MNP@BQR@A2-EXO-siGPX4 is a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered EXO for GBM therapy. | [220] |
| NIR830-RGD- ultrafine iron oxide nanoparticles (uIONP)/SN38 | RGD | αvβ3 | ultrafine iron oxide nanoparticles | GBM | NIR830-RGD-uIONP/SN38 exerted tumor-specific cytotoxicity on U87MG GBM cells and prolonged the survival of GBM mice. | [221] |
| NBP-loaded cerium oxide nanoparticles (NBP–CeO2 NPs) | / | / | Dl-3-n-butylphthalide (NBP) | ischemic stroke | NBP-CeO2NPs have antioxidant and neurovascular repair abilities. | [222] |
| magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for 5-iodo-2-deoxyuridine (IUdR) | / | / | IUdR | glioma | In addition to the high accumulation of IUdR/MNPs at targeted tumor sites, IUdR/MNPs demonstrated the ability of IUdR/MNPS to significantly enhance radiosensitizing effect, improve therapeutic efficacy, and increase toxicity in glioma-bearing rats. | [223] |
| Zinc oxide-nanoparticle (ZnO-NP) | / | / | ZnO-NP | neuroblastoma | Brain delivery of ZnO-NP is a potential therapeutic approach for neurodegenerative diseases. | [224] |
| PTX/R-flurbiprofen-PLGA-NPs | / | / | PTX; R-flurbiprofen | GBM | PLGA NPs can effectively carry their payload to glioma tissue, and the combination of anticancer and anti-inflammatory drugs can exert additional anti-tumor activity. | [225] |
| dual-targeted magnetic mesoporous silica nanoparticle (HA-MMSN-1F12) through surface-coupled Aβ42-targeting antibody 1F12 and CD44-targeting ligand hyaluronic acid (HA) | HA | antibody 1F12 and CD44 | anti-Aβ monoclonal antibody (mAb) | AD | HA-MMSN-1F12 facilitated mAb transit across the BBB and enhanced the ability of mAb to depolymerize Aβ aggregates into monomers. | [226] |
| Dopamine-loaded poly (butyl cyanoacrylate) nanoparticle (DA-PBCA NPs) | / | / | DA | PD | Da-pbca NPs can increase the release of DA in the brain and improve the brain structure and behavioral function in the PD rat model. | [227] |
| Chitosan-coated selenium nanoparticles (Cs-SeNPs)+ 5-fluorouracil (5-FU) | / | / | 5-FU | Brain Cancer (such as GBM) | Cs-SeNPs can effectively inhibit the proliferation, migration and invasion of GBM cells. The application of Cs-SeNPs can improve the sensitivity of GBM cells to 5-FU. | [228] |
| covalently conjugated hydroxyl PAMAM dendrimer–siGFP (D-siGFP) | GSH | GSHR | siGFP | GBM | D-siGFP is able to protect the siRNA payload from plasma proteins and endonucleases. | [229] |
| Temozolomide-conjugated gold nanoparticle functionalized with an antibody against the ephrin type-A receptor 3 (anti-EphA3-TMZ@GNPs) | anti-EphA3 | EphA3 | TMZ | GBM | anti-EphA3-TMZ@GNPs can be used as an intranasal delivery system to effectively treat GBM. | [230] |
| DOX-A2- carboxymethyl chitosan nanogel (CMCSN) | A2 | LRP1 | DOX | GBM | the strategy of combining the A2 and marine polysaccharide CMCS for brain targeting will have a promising application in GBM treatment. | [231] |
| Salinomycin- polyethylenimine-polyethylene glycol- iron oxide nanoparticles (Sali-PEI-PEG-IONPs) | / | / | Salinomycin | GBM | Sali-PEI-PEG-IONPs in combination with permeability enhancers such as hypertonic mannitol and external magnetic fields can provide effective and site-specific magnetic targeting for GBM chemotherapy. | [232] |
| iron oxide magnetic nanoparticles (NPs) as carrier system for helianthin (He/NPs) | / | / | helianthin | GBM | Helianthin-coated NPs were cytotoxic to GBM cells in vitro. | [233] |
| synthetic protein nanoparticles (SPNPs) coated with the transcytotic peptide iRGD (AMD3100-SPNPs) | / | / | AMD3100 | glioma | AMD3100-SPNP blocks CXCL12/CXCR4 signaling in vitro, Inhibition of GBM proliferation, reduction of CXCR4 monocyte myeloid-derived suppressor cells infiltration into the TME, restoration of BBB integrity, as well as induction of immunogenic cell death sensitize the tumor to radiotherapy and lead to anti-GBM immunity. In addition, the combination of AMD3100-SPNPs with radiation resulted in long-term survival. | [234] |
| gold nano-architectures- human serum albumin-DOX (NA-HSA-Dox) | / | / | DOX | Diffuse Intrinsic Pontine Glioma | NA-HSA-Dox has a better anti-tumor effect. | [235] |