过表达CD24的工程化外泌体药物递送载体的构建及初步安全性评价OA

Objective To construct engineered exosomes drug delivery carriers with membrane surface overexpression of CD24 molecules(CD24),investigate their in vivo distribution and metabolism,and conduct a preliminary in vivo safety evaluation.Methods CD24 expression plasmids were constructed using two strategies to obtain the corresponding engineered exosomes,CD24L exo and CD24-EGFP exo.The exosome marker proteins,particle size,and morphological characteristics were characterized.The in vivo distribution and metabolic characteristics of CD24L exo were explored through in vivo distribution experiments,and the safety of the engineered exosomes was evaluated.Results The engineered exosome CD24L exo with overexpression of CD24 on the membrane surface was successfully prepared.Compared with Control exo,there were no significant differences in marker proteins,peak particle size,or shape.CD24L exo was distributed in various organ tissues of mice,and the fluorescence intensity in vivo was significantly higher than that of Control exo at 48 hours(P<0.01).Continuous administration of 100 μg CD24L exo for 12 days did not cause damage to the vital organs of mice.Conclusion CD24L exo was successfully constructed,demonstrating enhanced immune evasion capability,prolonged in vivo retention time,and favorable preliminary safety compared to Control exo.