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

From: Stem cell-derived extracellular vesicles: role in oncogenic processes, bioengineering potential, and technical challenges

Engineering approach Examples Advantages Disadvantages References
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]