A biomimetic solution, albumin–doxorubicin molecular complex, targeting tumor and tumor-draining lymph nodes†

Abstract

Chemotherapy-induced immunologic cell death is haunted by the non-specific distribution of chemotherapeutic drugs and insignificant immune activation effects, which render efforts to inhibit the distant metastasis of tumors frustrated. Given the pivotal role that lymph nodes play in tumor metastasis, it is of vital importance whether the drug delivery to tumor-draining lymph nodes (TDLNs) succeeds. In the current study, we developed a doxorubicin–albumin complex (DOX–HSA) solution with the specific ability to simultaneously target the primary tumor and the TDLNs. DOX–HSA could effectively activate and amplify the immunogenic cell death (ICD) effect in both the tumor tissues and the TDLNs, resulting in increased release of damage-associated molecular patterns (DAMPs), which further promoted phagocytosis and maturation of dendritic cells (DCs), stimulated activation of CD8⁺T cells, and then significantly enhanced the therapeutic effects of doxorubicin on orthotopic 4T1 tumor-bearing model mice. Therefore, the DOX–HSA solution demonstrated a more prominent ability to control cancer cells and curb metastasis, as well as improved security by reducing cardiotoxicity and myelosuppression toxicity of doxorubicin itself. This DOX–HSA strengthened the synergistic anti-tumor effects based on the ICD effect in combination with traditional chemotherapy, thus providing promising prospects for clinical application.