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Table 4 Indirect modification of extracellular vesicles (EVs) (pre-isolation modification)

From: Application of engineered extracellular vesicles for targeted tumor therapy

Modification method

Parent cells

Strategy

Drug loaded

Application

References

Genetic engineering

Dendritic cells

Fusion of Lamp2b-expressing engineered mouse immature dendritic cells with the IRGD peptide to produce tumor-targeting EVs

DOX

Targeting of tumor tissue and inhibition of tumor growth

[203]

HEK293 cells

Donor cells were designed to express the transmembrane region of the platelet-derived growth factor receptor fused to Ge11 peptides to achieve tumor targeting treatment

Let-7a miRNA

Enhancement of tumor targeting and the antitumor effect of EVs

[212]

Metabolic engineering

B16F10 cells

Combining metabolic markers of newly synthesized proteins or glycoproteins from EV-secreting cells with reactive azide and bio-orthogonal click splicing

Streptavidin–HRP

Delivery of various anti-biotin protein fusions or biotin-coupled drugs

[113]

Membrane engineering

Not mentioned

Coupling of EVs containing azide lipids to targeted peptides by copper-free click chemistry

PTX

Enhancing the targeting effect of EVs against cancer cells

[76]

Loading contents in parent cells

HEK293T cells

The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. Enhanced the EV load of pre-miR-199a containing a modified TAR RNA loop using TAT peptide/HIV-1 TAR RNA-interacting peptide

miRNA

Improvement of the drug delivery efficiency of EVs

[114]

  1. DOX doxorubicin, EV extracellular vesicle, HIV human immunodeficiency virus, HRP horseradish peroxidase, IRGD internalizing RGD, Lamp2b lysosome-associated membrane glycoprotein 2b, miRNA microRNA, PTX paclitaxel, TAR trans-activation response, TAT trans-transcriptional activator