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Table 1 Surface-displayed proteins of EVs for targeted therapy

From: Nanoengineering facilitating the target mission: targeted extracellular vesicles delivery systems design

Protein on the surface of EV

Targeting peptide

Parent cell

Function

Effect

Measures of targeting efficiency

Refs.

Lamp-2b

RVG

Primary immature Dendritic cells

Alleviate Alzheimer’s disease

Central nervous system specific RVG binds specifically to acetylcholine receptor

Confocal laser imaging colocalization

[24]

RGD

Leukemia cell line K562

Promoted therapeutic angiogenesis

Overexpression of αvβ3 integrin on the surface of blood vessels, which specifically binds to RGD peptide

Targeted metabolic labeling technique

[107]

IMTP

BMSC

Enhanced vasculogenesis, and cardiac function

IMTP modified EVs can preferentially target ischemic myocardium

Near-Infrared Fluorescence Tracer

[108]

CMP

CDCs

Modulating the cardiac remodeling

CMP modified EVs can preferentially target cardiomyocyte

Whole-organ fluorescence imaging

[109]

RGE

Raw264.7

Inhibit glioma

Cross the BBB smoothly, accurately identify gliomas

Fluorescence imaging

[110]

CAP

Dendritic cells

Alleviate OA progression

CAP peptide modified EVs can specifically target chondrocytes

Near-Infrared Fluorescence Tracer

[25]

T7

HEK293T cells

Treatment of glioblastoma

T7 peptide has a higher efficiency of brain targeting than RVG peptide

Fluorescence imaging

[111]

tLyP-1

HEK293T cell

Treatment for non-small cell lung cancer

tLyP-1 peptide can selectively target nerve NRP1 and NRP2

–

[112]

E7

Dendritic cells

Alleviate OA progression

E7 peptide can target SF-MSC

Fluorescence imaging

[113]

IL-3

HEK293T cell

Improve prognosis in CML patients

IL-3 can specifically bind to IL-3R overexpressed in CML

Fluorescence imaging

[114]

 

Her2-binding affibody

HEK293T cell

Reverse the drug resistance in colorectal cancer

Her2-binding affibody binds to Her2 overexpressed on the surface of HCT-1165FR cancer cells

Fluorescence imaging

[46]

PDGFR

GE11

HEK293T cell

Deliver let-7a to breast cancer tissues that highly express EGFR

The specific binding ability of GE11 peptide to cancer cells overexpressing EGFR is better than EGF

In vivo imaging system monitoring

[104]

CD63

myostatin propeptide

NIH3T3

Treatment for DMD

Propeptide can be anchored on the surface of EVs via CD63

Flow cytometric analysis

[115]

OVA antigen

293-F cells

Improving DNA vaccine immunogenicity

OVA antigen fused to CD63 plasmid to produce EVs of antigen carriers that target CD8+ T cells to enhance immune response

–

[116]

  1. RVG, Rabies viral glycoprotein; RGD, L-Asparticacid, L-arginylglycyl; IMTP, Ischemic myocardium-targeting peptide; BMSC, Bone Marrow Stromal Cells; CDCs, Cardiosphere-derived cells; CMP, Cardiomyocyte specific peptide; Raw264.7, Leukemia cells in mouse macrophage; BBB, Blood–brain barrier; CAP, Chondrocyte-affinity peptide; OA, Osteoarthritis; HEK293, Human embryonic kidney 293; SF-MSC, Synovial fluid-derived mesenchymal stem cells; NRP1, Neuropilin1; NRP2, Neuropilin2; IL3, Interleukin 3; CML, Chronic myeloid leukemia; HCT-1165FR, 5-FU-resistant derivative of the HCT-116 human colon cancer cell line; EGFR, Epidermal growth factor receptor; EGF, Epidermal growth factor; DMD, Duchenne muscular dystrophy; TRAIL, TNF-related apoptosis-inducing ligand