Engineered delivery platform based on bacterial outer membrane vesicles for efficient labeling of 131I and improved radio-immunotherapy

Abstract

Radioisotope therapy (RIT) is one of clinical treatment for tumors, which can not only directly kill tumor cells, but also enhance anti-tumor immune response by inducing tumor cell immunogenic cell death (ICD). However, significant challenges for RIT are the low radiolabeling efficiency, as well as tumor targeting issues. Bacterial outer membrane vesicles (OMVs), which are natural nano-vesicles secreted by Gram-negative bacteria, are now garnering significant attention in cancer therapy due to their tumor-targeting and immunotherapeutic potential. Herein, we construct an engineering delivery platform based on OMVs to achieve efficient labeling of radioactive iodine and improve radio-immunotherapy (131I-STATH-OMV-PEG). Firstly, high tyrosine-rich protein statherin (STATH) is integrated onto the surface of OMVs (STATH-OMV) through bioengineered technology. The obtained STATH-OMV is coated with polyethylene glycol (PEG) and then labeled with radionuclide iodine-131 (131I-STATH-OMV-PEG), which exhibit excellent radiolabeling efficiency due to the integration of STATH. More importantly, 131I-STATH-OMV-PEG could also boost DC maturation and produce anti-tumor cytokines, thereby enhancing the systemic anti-tumor immune response induced by RIT. Additionally, 131I-STATH-OMV-PEG could inhibit orthotopic colon cancer, induce systemic immune memory effect and prevent tumor invasion. In summary, this study proposes an OMV-centered RIT delivery system that ensures proficient labeling of 131I, thereby amplifying the therapeutic effect of RIT and opening up a promising approach for tumor radio-immunotherapy.