Table 4 Methods and strategies for the modifications of EV surfaces

Genetic engineering

Infection with PGMLV-PA6 virus expressing both the CXCR4 protein and GFP

MSCs

Allowed more MSC-derived exosomes to nest around the target region

[139]

Transfection via the pCDH-GFP vector

HuCMSCs

Decreased ATP concentration; increased adenosine levels; and reduced spinal cord inflammation

[140]

Transfection via the recombinant adenoviral vector GFP-CTF1 encoding CTF1

BMSCs

Increased proangiogenic activity and the rates of successful pregnancy outcomes

[141]

Transfection via a pCDNA-MEG3 vector

OS cells

Inhibition of osteosarcoma growth

[143]

Introduction of pcDNA3.1(-)-RGD-Lamp2b into cells by electroporation

HEK293T

Enhanced tumor site targeting

[145]

Transfection via a miR-31-5p lentiviral vector

HEK293

Promoted the healing of diabetic wounds

[144]

Co-transfection of a reporter plasmid and miR-181b mimics using Lipofectamine

Human umbilical cord mesenchymal stem cells (HuCMSCs)

Enhanced M2 polarization; inhibited inflammation; and promoted osseointegration

[244]

Transfection via an XStamp-PDGFA lentiviral vector

Neural stem cells (NSCs)

Improved potential for CNS injury targeting

[245]

Transfection via an LV-iRGD-Lamp2b lentiviral vector

Human cord blood MSCs (cbMSCs)

Enhanced targeting to tumor sites

[246]

Transfection via a Lenti-XStamp-PDGFA lentiviral vector

Neural stem cells (NSCs)

Enhanced targeting efficiency for central nervous system lesions

[247]

Transfection via the pRBP-Lamp2b-HA-hygro vector using Lipofectamine 2000

HEK293 cells

Anti-inflammatory effects

[248]

Transfection via the iRGDC1-EGFP-Lamp2b virus

HEK293T

Enhanced tumor targeting

[249]

Bioorthogonal chemistry

The azide groups were bioorthogonally labeled with DBCO-Cy5 via bioorthogonal click chemistry

A549

Exosome tracking and imaging

[148]

DBCO reacted with azide or azide-containing methionine analogs via bioorthogonal click chemistry

B16F10

Regulation of exosome composition and binding of exosomes for intracellular delivery

[147]

DBCO-Exo was linked to a c(RDGyK) peptide with an azide moiety via copper-free click chemistry

MSCs

Improved targeting of lesion sites

[149]

Copper-free click chemistry was used with AlexaFlour®488 (AF488)-azide

PANC-1

B16F10

HEK293

Achieved quantification of intracellular tracking and intracellular uptake

[150]

Physical modification

Membrane extrusion method

HCC

Enhanced targeting ability and improved siRNA transfection efficiency

[153]

Lipid membrane fusion

Sf9 insect cells

Enhanced targeting capabilities

[154]

Membrane extrusion method

SKOV3-CDDP

Enhanced targeting capabilities

[155]

Membrane extrusion method

L-929

Depleted cells and homing effects

[156]

Membrane fusion technology using the freeze–thaw method

CT26

Allowed immune evasion, enhanced targeting ability, and acted as a drug carrier

[157]

PEG-mediated membrane fusion

HUVECs

Widely used in studies on the mechanism of membrane fusion

[158]

Membrane extrusion method

J774A.1

Enhanced targeting ability and acted as a drug carrier

[159]

Incubation-mediated membrane fusion

HEK293FT

Enabled efficient wrapping of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in exosomes

[250]

Incubation

HEK293T

Improved targeting capabilities

[251]

Electrostatic interaction

MSCs

Targeted hepatocyte asialoglycoprotein receptors

[160]

Extrusion method

Bone marrow MSCs

Improved targeting ability and promoted angiogenesis

[161]

Chemical modification

Bioconjugate chemistry

Human leukemia monocytic cell line (THP-1)

Promoted blood–brain barrier penetration and improved targeting

[164]

Copper-free click chemistry

M2-BV2

Provided rapid and effective recruitment and differentiation transformation of neural stem cells

[165]

Cycloaddition reaction of sulfonyl azide

U-87 MG

Improved targeting

[166]

Hydrophobic insertion method

ADMSCs

Improved targeting

[167]

Lipid insertion method

BMSCs

Improved targeting

[168]

PDA self-polymerization and thiol-Michael addition reactions

L929

Facilitated fluorescent labeling

[169]

Hydrophobic interaction (lipid insertion method)

MSCs derived from human induced pluripotent stem cells (iPSCs)

Improved targeting

[170]

Thiol-maleimide click reaction

Milk

Facilitated fluorescent labeling and improved targeting

[171]

Phospholipid insertion method

Primary human adipose-derived stem cells

Improved targeting

[252]

Phospholipid insertion method

Milk

Improved targeting

[253]

Phospholipid insertion method

HepG2

Photothermal effects and improved targeting

[254]

EDC/NHS chemistry

MSCs

Improved targeting

[255]

Membrane anchoring

B16F10

Improved targeting and imaging capabilities

[256]

Lipid-anchoring method

BMDCs

Improved specificity for T cells

[257]