Enhancing Chemotherapy Efficacy via an Autologous Erythrocyte-Anchoring Strategy with a Closed-System Drug-Transfer Device

Chemotherapeutic drugs often fail to localize efficiently to tumors when administered intravenously, causing off-target effects. This study proposes an autologous erythrocyte (ER)-anchoring strategy to improve chemotherapy efficacy and reduce side effects. Utilizing a modified hemodialysis instrument, a closed-system drug-transfer device was developed for autologous ER procurement and immunogenicity mitigation. Doxorubicin (DOX) and indocyanine green (ICG) were encapsulated in autologous ERs and then modified with DSPE-PEG-FA. The final product, DOX-ICG@ER-D, was reintroduced into circulation to enhance chemotherapy. These obtained DOX-ICG@ER-D showed good stability, minimal cardiotoxicity, and extended circulation time. Compared to free DOX, DOX-ICG@ER-D had a higher accumulation of DOX in hepatocellular carcinoma and the release of DOX could be controlled by laser irradiation. Tumor-bearing rats treated by these DOX-ICG@ER-D demonstrated improved antitumor efficacy and reduced cardiotoxicity. Thus, this autologous ER-anchoring strategy offers a promising alternative to intravenous chemotherapy in the clinic.