Aptamer-Based Erythrocyte-Derived Mimic Vesicles Loaded with siRNA and Doxorubicin for the Targeted Treatment of Multidrug-Resistant Tumors.

Multidrug resistance (MDR) remains one of the most important challenges to clinical chemotherapeutics. In this study, versatile mimic vesicles (MVs) derived from erythrocytes were investigated as delivery systems for siRNA and doxorubicin (DOX) to treat MDR tumors. The carriers could be readily obtained through extruding erythrocyte membranes and had the advantages of biological homogeneity, high output, controllable size, low cost, and excellent biocompatibility. Moreover, aptamers modified on the MVs endowed the carriers with tumor-targeting capacity. DOX and P-glycoprotein (P-gp) siRNA were loaded onto the MVs through incubation and cholesterol-mediated methods, achieving high loading rates and targeted tumor delivery. The drug-loaded carriers could successfully overcome drug resistance and synergistically kill MDR tumors through P-gp silencing and DOX-induced growth inhibition. This MV-based drug delivery system therefore provides new insights into the synergistic targeting of MDR tumors and offers an alternative delivery strategy to overcome MDR.