Aptamer Circuit‐Engineered Bio‐Nanovesicles With Self‐Promoted Tumor‐Targeting Loop for Efficient Immunogenic Chemotherapy

Targeted delivery of chemodrugs to tumor sites is highly desirable for efficient chemotherapy. Extracellular vesicles (EVs)-based carrier is an ideal candidate for drug delivery in cancer therapy. However, the insufficient tumor-targeting capability remains to be solved. Herein, we designed an aptamer circuit with cascade recognition capacity to guide the vesicles for tumor targeting. The sequential signal transduction triggered by the specific binding between aptamers and their targets leads to the preferential binding of vesicles with cancerous cells rather than noncancerous cells with fewer targets. Moreover, a self-promoted tumor-targeting loop induced by Doxorubicin Hydrochloride (DOX) released from vesicles further amplified the targeting capability of the vesicle-based drug carrier to tumor sites through up-regulating PDL1 marker on the surface of tumor cells. Ultimately, the accumulation of DOX in tumor cells resulted in the immunogenic cell death (ICD) for evoking anti-tumor immune response. Overall, this work presents a self-promoted tumor-targeting strategy for vesicle-based carrier by coupling the cascade recognition and tumor-targeting loop, which improves the therapeutic effect of immunogenic chemotherapy.