Biomimetic Nanoerythrosome‐Coated Aptamer–DNA Tetrahedron/Maytansine Conjugates: pH‐Responsive and Targeted Cytotoxicity for HER2‐Positive Breast Cancer

Abstract

DNA materials have emerged as potential nanocarriers for targeted cancer therapy to precisely deliver cargos with specific purposes. The short half‐life and low bioavailability of DNA materials due to their interception by the reticuloendothelial system and blood clearance further limit their clinical translation. This study employs an HER2‐targeted DNA‐aptamer‐modified DNA tetrahedron (HApt‐tFNA) as a drug delivery system, and combines maytansine (DM1) to develop the HApt‐DNA tetrahedron/DM1 conjugate (HApt‐tFNA@DM1, HTD, HApDC) for targeted therapy of HER2‐positive cancer. To optimize the pharmacokinetics and tumor‐aggregation of HTD, a biomimetic camouflage is applied to embed HTD. The biomimetic camouflage is constructed by merging the erythrocyte membrane with pH‐responsive functionalized synthetic liposomes, thus with excellent performance of drug delivery and tumor‐stimulated drug release. The hybrid erythrosome‐based nanoparticles show better inhibition of HER2‐positive cancer than other drug formulations and exhibit superior biosafety. With the strengths of precise delivery, increased drug loading, sensitive tumor probing, and prolonged circulation time, the HApDC represents a promising nanomedicine to treat HER2‐positive tumors. Notably, this study developsa dual‐targeting nanoparticle by combining pH‐sensitive camouflage and HApDC, initiating an important step toward the development and application of DNA‐based medicine and biomimetic cell membrane materials in cancer treatment and other potential biological applications.