Extracellular vesicles （EVs） are small membrane-bound vesicles released by cells, typically ranging from 50 to 1000 nanometers in diameter. Among them, small extracellular vesicles （sEVs） are less than 200 nanometers in diameter and participate in various physiological and pathological processes. Tumor-derived small extracellular vesicles （TDsEVs） have recently attracted considerable attention due to their ability to influence tumor formation and metastasis. Compared with conventional liposomes used in cancer therapy, TDsEVs exhibit stronger homing ability, higher permeability across biological barriers, and lower immunogenicity, thereby enhancing the precision and efficiency of drug delivery. However, TDsEVs contain oncogenic proteins that may pose safety risks and must be thoroughly removed. In this study, TDsEVs derived from pancreatic cancer cells were treated using electroporation and other approaches to eliminate internal oncogenic components. The ultra-sensitive eSimoa platform was employed to evaluate the clearance efficiency and the integrity of EV membranes, verifying the complete removal of oncogenic proteins. Ultimately, the cleared TDsEVs are expected to demonstrate improved safety and drug-loading capacity, offering a novel carrier system for targeted cancer therapy.