(2024) 22:18 | Zhen Chen1,2,3, Min Xiong4, Jiaqi Tian1,2, Dandan Song1,2, Shuyin Duan5 and Lin Zhang1,2*
Exosomes, nanoscale extracellular vesicles, have emerged as promising drug delivery vehicles due to their biocompatibility and low immunogenicity. However, their clinical potential is limited by short circulation half-lives, variability based on cell source, and insufficient drug loading capacity. To address these limitations, researchers have developed engineered exosomes through genetic modification, enhancing drug encapsulation and targeting. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, including techniques for assessing exosome drug loading, release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes. The review also highlights the latest applications of exosome engineering in clinical translation, emphasizing the need for robust characterization methods and reporting standards to accelerate the development of exosome engineering technologies and pave the way for clinical studies. Key topics include exosome isolation, purification, and drug loading methods, as well as strategies for decorating exosomes with targeting ligands and modulating endogenous proteins to enhance their therapeutic efficacy. The review concludes by discussing the assessment criteria and evaluation methods for drug encapsulation in exosomes, including laboratory testing, cell experiments, animal models, and clinical applications in cancer and neurological diseases.Exosomes, nanoscale extracellular vesicles, have emerged as promising drug delivery vehicles due to their biocompatibility and low immunogenicity. However, their clinical potential is limited by short circulation half-lives, variability based on cell source, and insufficient drug loading capacity. To address these limitations, researchers have developed engineered exosomes through genetic modification, enhancing drug encapsulation and targeting. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, including techniques for assessing exosome drug loading, release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes. The review also highlights the latest applications of exosome engineering in clinical translation, emphasizing the need for robust characterization methods and reporting standards to accelerate the development of exosome engineering technologies and pave the way for clinical studies. Key topics include exosome isolation, purification, and drug loading methods, as well as strategies for decorating exosomes with targeting ligands and modulating endogenous proteins to enhance their therapeutic efficacy. The review concludes by discussing the assessment criteria and evaluation methods for drug encapsulation in exosomes, including laboratory testing, cell experiments, animal models, and clinical applications in cancer and neurological diseases.