Ultrasound-responsive erythrocyte-fused vesicles for targeted theranostics of Wilms’ tumor

Wilms’ tumor (WT) is the most common renal tumor of childhood. Despite clinical chemotherapy and radiotherapy showed favorable treatment-response, serious side effects caused by the absence of efficient targeted therapeutic fumulations remain a major challenge in clinical practice. Here, we identified neural cell adhesion molecule 1 (NCAM1) as a potential delivery target by bioinformatic analysis and selected an NCAM1-targeting peptide (NTP) as its specific ligand. Then, we prepared NTP-modified vesicles loaded with doxorubicin (DOX) and perfluorohexane (PFH) (NDP), which were fused with red blood cell (RBC) membranes to obtain NDP@RBC, where “@RBC” denotes fusion with RBC membranes. After administration, the RBC membrane prolonged the circulation time of NDP@RBC, with 10.95% of baseline fluorescence retained at 48 h, compared with undetectable levels for free DOX and NDP. The NTP significantly facilitated WT cell recognition and cellular uptake, with the mean fluorescence intensity at 2 h reaching 0.95 × 10 5 compared with 0.62 × 10 5 or the non-targeted DP@RBC group. PFH encapsulated in the vesicles enhanced the ultrasound (US) imaging signal and mediated ultrasound-responsive drug release, with cumulative DOX release reaching 85% under ultrasound versus 13.3% without ultrasound at 60 min. In vivo animal experiments showed that NDP@RBC + US suppressed tumor growth, with a tumor growth inhibition rate of 80.22% compared with the PBS group and 19.27% compared with NDP@RBC alone. In summary, this work highlights the importance of targeted theranostics of WT.