HER2-Specific Reduction-Sensitive Immunopolymersomes with High Loading of Epirubicin for Targeted Treatment of Ovarian Tumor

Monoclonal antibodies can effectively target to tumors in patients, as validated by antibody–drug conjugates (ADCs). The clinically used ADCs, nevertheless, are restricted to toxins only and suffer from low drug content, excessive use of antibody, and high cost. Here, we report on trastuzumab-decorated disulfide-cross-linked polymersomes (Tra-Ps) for specific delivery of epirubicin hydrochloride (EPI·HCl) to HER2-positive SKOV-3 ovarian tumor. EPI·HCl-loaded Tra-Ps (Tra-Ps-EPI) with a small size of 50–60 nm and varying Tra surface densities (0.5 to 2.4 Tra per Ps) were conveniently obtained via post-conjugation of thiolated trastuzumab onto the surface of maleimide-functionalized Ps-EPI with a drug loading content of 12.7 wt %. Interestingly, Tra-Ps with 1.3 trastuzumab on the surface exhibited a 6-fold higher binding affinity to the HER2 extracellular domain than that of native trastuzumab. In vitro studies revealed that Tra-Ps-EPI with long-term storage stability could rapidly release drugs under a redu...