Table 3 Typical nanocarriers for treatment of IS

Polymeric nanoparticles

Glutathione-coated PLGA-b-PEG

Thyroid hormones (T3)

Glutathione

Protect brain against ischemic injury

[89]

Cationic lipid assisted PEG-PLA

C3-siRNA

_

Inhibit microglial neurotoxicity

[90]

Chitosan

bFGF and z-DEVD-FMK

Transferrin

Reduce infarct volume in brain

[92]

Tween80 coated chitosan-NIPAAM

Riluzole

_

Protect brain against ischemic injury

[93]

_

Melanin

_

ROS scavenging and anti -inflammation-related

[96]

Polymeric micelles

Copolymer PEG-b-(PELG-g-PLL)

TNF-α

Attenuate the oxidative stress injury, the inflammation-related activity and the apoptosis level in I/R-induced cerebral injury

[104]

Agonistic micelles

Edaravone

_

Regulate the BBB permeability

and deliver neuroprotectants

[105]

Dendrimers

Arginine ester of PAMAM

siRNA

_

Perform siRNA-mediation gene knockdown in brain

[112]

cationic PAMAM

_

_

Protect the injured brain from stroke by reaching the ischemic neurons

[110]

Nano-hydrogels

Alginate

VEGF

_

Induce significant functional and structural protection from ischemic injury

[119]

Liposomes

Phosphatidylethanolamine(PE), cholesterol, dicetylphosphate

CDP-Choline

_

Prevent age related global moderate cerebral ischemia reperfusion

[127]

PEG-coated inositol hexaphosphate

Hemoglobin

_

Reduce ischemia reperfusion injury

[128]

DPPC and cholesterol

Urokinase

Cyclic RGD

Improve the thrombolytic efficacy

[129]

DPPC, cholesterol,

PEG₂₀₀₀-PE

Minocycline

_

Reduce TNF-α induced MMP-9

release

[132]

DSPC, DPPC, cholesterol,

DSPE-PEG₂₀₀₀

FK506 (Tacrolimus)

_

Reduce cerebral cell apoptosis and ameliorate motor function deficits

[133]

DPPC, Egg-PC, DPPG, cholesterol, PEG₂₀₀₀-PE

Xenon (Xe)

_

Reduce infarct size in brain

[135]

Bean lecithin, cholesterol, DSPE-PEG₂₀₀₀

ZL006

Stroke homing

peptide (SHp) and T7 peptide

Block nNOS-PSD-95 association and reduce infarct size in brain

[140]

Solid lipid nanoparticles

Monostearin, medium-chain triglyceride,

polyethylene glycol

monostearate

3-n-Butylphthalide

Fas ligand

antibody

Improve brain injury and neurological function

[145]

tripalmitin, Gelucires, vitamin E, phospholipids, and poloxamer 188

Baicalein

improve baicalein's stability and the ability of baicalein to penetrate the brain

[146]

PEGylated cationic solid lipid nanoparticles

Baicalein

OX26

elevate biological availability of baicalin in cerebral spinal fluid of mice under the cerebral ischemia–reperfusion injury

[147]

Inorganic nanocarriers

Silica-coated superparamagnetic iron oxide

Endothelial progenitor cells (EPCs)

_

Improve neurobehavioral outcomes and reduce brain atrophic volume

[151]

_

Amino-modificated carbon nano-scale tubes (CNTs)

_

Decrease cell apoptosis in the brain area

[162]

Silica-coated Au or lipophilic polyaspartic acid-based polymer

Vitamin C

_

ROS scavenging

[163]

_

Platinum

_

ROS scavenging

[164]

_

Cerium oxide

_

ROS scavenging

[166]

Cell-derived biomimetic nanocarriers

Exosomes purified from BM-MSCs

microRNAs (miRNAs)

RVG-Lamp2b

Target delivery of gene drugs to the brain for ischemic brain

[174]

Exosomes purified from BM-MSCs

Curcumin

c(RGDyK) peptide

Target delivery of curcumins to the brain for ischemic brain

[175]

Mesenchymal stem cells (MSCs)

MiR-133b

Palmitic acid-peptide

Target delivery of miR-133b to increase the expression level in an ischemic lesion and further improve curative effects

[176]

Dextran polymer core modified with RBC membrane shell

NR2B9C

Stroke homing

peptide (SHp)

Reduce ischemia reperfusion injury

[180]

Mn₃O₄@nanoerythrocyte

_

T7

Remodel the stroke microenvironment through self-adapted oxygen regulating and free radical scavenging

[181]

γ-Fe2O3 magnetic nanoparticles inspired by natural platelets

L-arginine

_

Target adhesion to the injured brain blood vessel during formation of thrombus

[184]

Acetal Modified Dextran modified with platelet membrane shell

ZL006e and tPA

Cell-penetrating peptide

Enhance the treatment of thrombolytics and neuroprotectant for IS

[185]

Neutrophil-mediation cross-linked dendrigraft poly-L-lysine (DGL) nanoparticles

Catalase

PGP ligands

Protect the catalase enzymatic activity from degradation and well transport to receiver cells

[188]

Neutrophil membrane-derived nanovesicles

Resolvin D2 (RvD2)

_

Enhance resolution of inflammation, thus protecting brain injury during IS

[189]

Neutrophils-derived liposomes system

Puerarin

-

Enhance the neuro-protection effect at the ischemic penumbra

[190]

Other functional nanocarriers

Copolyoxalate

(H₂O₂-responsive)

Vanillyl alcohol(VA)

_

Exert anti-inflammation-related and anti-apoptotic activities

[191]

B-PDEA

(ROS-responsive)

Neural stem cells (NSCs)

_

Lead to efficient expression of brain derived neurotrophic factors

[192]

PLA-coated mesoporous silica

(ROS-responsive)

Resveratrol

Low-density lipoprotein receptor (LDLR)

Enhance the transcytosis across the blood–brain barrier

[193]

Methoxy poly(ethylene glycol)-poly(L-ethionine) diblock copolymers

(H₂O₂-responsive)

Rhodamine-6G

_

Serve as promising platforms for sustained drug delivery for diseases with local oxidative stress

[194]

Methoxy poly(ethylene glycol)-poly(β-amino ester) (PEG-PAE) with piperidine and imidazole rings

(pH-responsive)

Human serum albumin (HSA)

_

Target the acidic environment in brain

[196]

Poly (urethane amino sulfamethazine) (PUASM)

(pH-responsive)

Stromal cell derived from factor-1α

_

Modify the microenvironment to increase innate neurorestorative processes

[197]