Table 1 Summary of the different approaches in the engineering of EVs for precision cancer therapeutics

Overexpression of protein in parent cells

Rabies viral glycoprotein, CD63, GLUT4, HSPs, BDNF, CD24, EpCAM, CD3, SMPD2, HIF-1α

Enhanced cargo loading, efficient delivery, relatively simple, biocompatible, stable expression

Low transfection efficiency, contamination of non-transfected EVs, risk of genotoxicity

[51, 52, 57]

Antibody/antigen conjugation

CD9 antibody with Alexa-647, mCherry, photoreceptor cryptochrome 2, Nef-E7 fusion protein

Specific and easy to operate, targeted delivery, high therapeutic potential

May impair functionality, low loading efficiency, antigen immunogenicity

[50, 51, 55, 56]

Modification of surface proteins

Arg-Gly-Asp (RGD) peptide, Ac₄ManNAz, PDGFR

Easy, effective for delivery, fast and scalable production, extended half life

Compromise membrane integrity, may change surface area

[24, 52, 55, 58]

Synthetic modification

EMMPRIN, MHC-I and MHC-II

Greater tracking efficiency, high drug loading efficiency

Toxicity, washing required, potential deformation of membrane

[51, 52, 54, 58, 59]

Chemical modification

Glypican-1, c(RGDyK) peptides

Enhanced fusion efficiency, better conjugation, stable binding

Toxicity, may impair functionality, harsh chemicals involved

[51, 54, 56, 59]

Passive and active loading (sonication, incubation, electroporation)

Paclitaxel, imatinib, siRNA, doxorubicin

Simple, intact membrane, quick and efficient, simple protocol, chemical free

Aggregation, slow passive loading, low efficiency, untargeted release of drugs

[51, 52, 54,55,56,57]