Improving Tumor Accumulation of Aptamers by Prolonged Blood Circulation

Developing cancer targeted medicine depends on increasing delivery efficiency and tumor site accumulation of theranostic agents. To accomplish this, we report a modification of PTK7 receptor-specific aptamer Sgc8 with the small molecule Evans Blue (EB), thus implementing an albumin binding hitchhike strategy for prolonged blood circulation. The EB molecule could insert into the hydrophobic region of serum albumin and form an aptamer/albumin complex. This complex showed superior physiological stability, facilitating longer blood half-life, and maintaining its targeting capacity. Successful conjugation of EB-aptamers was confirmed by a series of characterization methods. Targeting performance was tested on a xenografted mouse tumor model. Taking advantage of the long circulating aptamer/HSA complex, improved accumulation, and delivery efficiency to the tumor site were achieved. Through ex vivo quantification of the EB-Sgc8 aptamers’ biodistribution, the mechanism of improved targeting performance was illuminated. Therefore, the increased aptamers tumor delivery efficiency and accumulation indicate that prolonging blood circulation is a promising strategy to improve aptamers’ targeted delivery performance in the future clinical translation.