Table 2 Examples of genetic engineering parental cells for surface modification of EVs

Lamp2b

RVG peptide

BACE1 siRNA

Delivery of BACE1 siRNA to brain neurons with great potential for Alzheimer’s therapy

[65]

HMGB1-siRNA

High brain accumulation, effective gene silencing in ischemic strokes

[92]

Opioid receptor mu siRNA

Delivery of siRNA to the central nervous system and restraining the morphine relapse

[109]

miR-124

Enhanced gene-drug delivery to the ischemic cortex of the brain and attenuating ischemic damage

[110]

Nerve growth factor protein and mRNA

Simultaneous delivery of nerve growth factor mRNA and protein to the ischemic cortex

[111]

mRNA (including nluc, catalase)

Delivery of cargo mRNA to the brain, for rescuing neurotoxicity and neuro-inflammation in Parkinson’s disease

[61]

circDYM

Amelioration of depression‐like behaviors

[112]

circSCMH1

Enhanced functional recovery in rodent and nonhuman primate ischemic stroke models

[113]

Aptamer F5R1 or F5R2

Decreased α-synuclein aggregates in the PD model

[114]

T7 peptide

Antisense miR-21 (AMO-21)

Delivery of AMO-21 into intracranial GBM

[38]

CAP peptide

miR-140

Penetration of the dense mesochondrium, inhibits cartilage degradation, and alleviats osteoarthritis progression

[116]

E7 peptide

Kartogenin

Enhanced chondrogenesis of synovial fluid-derived MSCs (SF-MSCs), and pronounced therapeutic effects in a rat osteoarthritis model

[117]

RGD peptide

miR-484

Improved vascular normalization, increased ovarian cancer sensitivity towards chemotherapy and prolonged survival time of the tumor-bearing mice after chemotherapy

[118]

SP94 peptide

Multi-siRNA against GPX4 and DHODH

Enhanced sorafenib-induced ferroptosis and increased hepatocellular carcinoma sensitivity to sorafenib

[119]

tLyp-1 peptide

Human Sox2 siRNA

Knock-down of Sox2 in cancer cells and reduced stemness of cancer stem cells

[120]

Her2 affibody

5-Fluorouracil and miR-21

Reversal of drug resistance in colorectal cancer and enhanced efficacy in cancer therapy

[121]

CD63

Apo-A1

miR-26a

Selective binding to HepG2 cells, upregulated miR-26a expression, and decreased cell migration and proliferation

[122]

CD9

ApoB

N.A

Prolonged retention in the brain

[123]

PDGFR

Ge11 peptide

Let-7a miRNA

Specific delivery of let-7a to xenograft cancer cells in RAG2^−/− mice

[95]

scFv antibodies against CD3 and EGFR

N.A

In vitro cytotoxicity towards EGFR-positive triple-negative breast cancer (TBNC) cells in the presence of nonactivated human peripheral blood mononuclear cells, and excellent antitumor activities in a mouse TBNC xenograft model

[125]

scFv antibodies against CD3 and EGFR, PD-1, OX40L

N.A

Robust anti-cancer immunity, and highly potent inhibition against established TNBC tumors in mice

[126]

Syntenin-1

N.A

Cytokine-binding domains derived from tumor necrosis factor receptor 1 and interleukin-6 signal transducer

Superior efficacy in several inflammatory mouse models

[129]

PTGFRN

N.A

Single-chain version of human interleukin-12

Prolonged tumor retention and great antitumor activity

[130]

CXCR4

CXCR4

TRAIL

Synergistic antitumor effects with carboplatin in the MDA-MB-231Br SCID mouse model

[131]

C1C2 domain of lactadherin

N.A

PSA and PAP

A striking increase in the immune response and improved antitumor efficacy in the tumor models

[133]

Anti-HER2 scFv antibody

HChrR6 mRNA

Successful and specific delivery of HChrR6 mRNA and near-complete growth-arrest of orthotopic BT474 xenografts in vivo

[134]

GPI anchor signal peptides of DAF

Anti-EGFR nanobodies

N.A

Improved EV binding to EGFR-expressing tumor cells

[135]